{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T22:06:42Z","timestamp":1770070002960,"version":"3.49.0"},"reference-count":152,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>Heterozygous autosomal dominant mutations in the CXCR4 gene cause WHIM syndrome, a severe combined immunodeficiency disorder. The mutations primarily affect the C-terminal region of the CXCR4 chemokine receptor, specifically several potential phosphorylation sites critical for agonist (CXCL12)-mediated receptor internalization and desensitization. Mutant receptors have a prolonged residence time on the cell surface, leading to hyperactive signaling that is responsible for some of the symptoms of WHIM syndrome. Recent studies have shown that the situation is more complex than originally thought, as mutant WHIM receptors and CXCR4 exhibit different dynamics at the cell membrane, which also influences their respective cellular functions. This review examines the functional mechanisms of CXCR4 and the impact of WHIM mutations in both physiological and pathological conditions.<\/jats:p>","DOI":"10.3389\/fimmu.2024.1406532","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T04:43:17Z","timestamp":1720154597000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["The complex nature of CXCR4 mutations in WHIM syndrome"],"prefix":"10.3389","volume":"15","author":[{"given":"Jos\u00e9 Miguel","family":"Rodr\u00edguez-Frade","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luis Ignacio","family":"Gonz\u00e1lez-Granado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u00e9sar A.","family":"Santiago","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Mellado","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1993.1251","article-title":"Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen","volume":"16","author":"Federsppiel","year":"1993","journal-title":"Genomics"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1089\/dna.1993.12.465","article-title":"Molecular cloning, characterization, and localization of the human homolog to the reported bovine NPY Y3 receptor: lack of NPY binding and activation","volume":"12","author":"Herzog","year":"1993","journal-title":"DNA Cell Biol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.8.4754","article-title":"Genomic organization and functional characterization of the chemokine receptor CXCR4, a major entry co-receptor for human immunodeficiency virus type 1","volume":"273","author":"Wegner","year":"1998","journal-title":"J Biol Chem"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1126\/science.272.5263.872","article-title":"HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor","volume":"272","author":"Feng","year":"1996","journal-title":"Science"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.2174\/1381612043452640","article-title":"Chemokines and their receptors as therapeutic targets: the role of the SDF-1\/CXCR4 axis","volume":"10","author":"Juarez","year":"2004","journal-title":"Curr Pharm Des"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/382833a0","article-title":"The CXC chemokine SDF-1 is the ligand for LESTR\/fusin and prevents infection by T-cell-line-adapted HIV-1","volume":"382","author":"Oberlin","year":"1996","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1515\/bmc-2014-0007","article-title":"CXCL14 antagonizes the CXCL12-CXCR4 signaling axis","volume":"5","author":"Hara","year":"2014","journal-title":"Biomol Concepts"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M116.717751","article-title":"Macrophage migration inhibitory factor-CXCR4 receptor interactions: EVIDENCE FOR PARTIAL ALLOSTERIC AGONISM IN COMPARISON WITH CXCL12 CHEMOKINE","volume":"291","author":"Rajasekaran","year":"2016","journal-title":"J Biol Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20111739","article-title":"HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4","volume":"209","author":"Schiraldi","year":"2012","journal-title":"J Exp Med"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1016\/j.dci.2011.01.019","article-title":"A family tree of vertebrate chemokine receptors for a unified nomenclature","volume":"35","author":"Nomiyama","year":"2011","journal-title":"Dev Comp Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.2210\/pdb3oe0\/pdb","article-title":"Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists","volume":"330","author":"Wu","year":"2010","journal-title":"Sci (1979)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"671","DOI":"10.3390\/vaccines11030671","article-title":"Structural and phylogenetic analysis of CXCR4 protein reveals new insights into its role in emerging and re-emerging diseases in mammals","volume":"11","author":"Naheed","year":"2023","journal-title":"Vaccines (Basel)"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/s41423-023-00974-6","article-title":"The chemokines CXCL8 and CXCL12: molecular and functional properties, role in disease and efforts towards pharmacological intervention","volume":"20","author":"Cambier","year":"2023","journal-title":"Cell Mol Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20072513","article-title":"CXCR4 is required for the quiescence of primitive hematopoietic cells","volume":"205","author":"Nie","year":"2008","journal-title":"J Exp Med"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20011284","article-title":"Hematopoietic stem cells are uniquely selective in their migratory response to chemokines","volume":"195","author":"Wright","year":"2002","journal-title":"J Exp Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.170.1.421","article-title":"Transgenic expression of stromal cell-derived factor-1\/CXC chemokine ligand 12 enhances myeloid progenitor cell survival\/antiapoptosis in vitro in response to growth factor withdrawal and enhances myelopoiesis in vivo","volume":"170","author":"Broxmeyer","year":"2003","journal-title":"J Immunol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20041385","article-title":"Rapid mobilization of murine and human hematopoietic stem and progenitor cells with AMD3100, a CXCR4 antagonist","volume":"201","author":"Broxmeyer","year":"2005","journal-title":"J Exp Med"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1992","DOI":"10.1038\/sj.leu.2402684","article-title":"The essential roles of the chemokine SDF-1 and its receptor CXCR4 in human stem cell homing and repopulation of transplanted immune-deficient NOD\/SCID and NOD\/SCID\/B2m(null) mice","volume":"16","author":"Lapidot","year":"2002","journal-title":"Leukemia"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1002\/stem.3174","article-title":"CXCR4 expression in the bone marrow microenvironment is required for hematopoietic stem and progenitor cell maintenance and early hematopoietic regeneration after myeloablation","volume":"38","author":"Singh","year":"2020","journal-title":"Stem Cells"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1402419","article-title":"CXCL12 regulates through JAK1 and JAK2 formation of productive immunological synapses","volume":"194","author":"Cascio","year":"2015","journal-title":"J Immunol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1038\/ni1100","article-title":"Germinal center dark and light zone organization is mediated by CXCR4 and CXCR5","volume":"5","author":"Allen","year":"2004","journal-title":"Nat Immunol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.neures.2015.10.001","article-title":"Increased stereotypy in conditional Cxcr4 knockout mice","volume":"105","author":"Cash-Padgett","year":"2016","journal-title":"Neurosci Res"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1038\/31261","article-title":"The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract","volume":"393","author":"Tachibana","year":"1998","journal-title":"Nature"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2008060640","article-title":"The CXCL12 (SDF-1)\/CXCR4 axis is essential for the development of renal vasculature","volume":"20","author":"Takabatake","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1146\/annurev.immunol.17.1.657","article-title":"Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease","volume":"17","author":"Berger","year":"1999","journal-title":"Annu Rev Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.62.6.2026-2032.1988","article-title":"Differential syncytium-inducing capacity of human immunodeficiency virus isolates: frequent detection of syncytium-inducing isolates in patients with acquired immunodeficiency syndrome (AIDS) and AIDS-related complex","volume":"62","author":"Tersmette","year":"1988","journal-title":"J Virol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1126\/science.8356453","article-title":"Genotypic and phenotypic characterization of HIV-1 patients with primary infection","volume":"261","author":"Zhu","year":"1993","journal-title":"Science"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/35065016","article-title":"Involvement of chemokine receptors in breast cancer metastasis","volume":"410","author":"M\u00fcller","year":"2001","journal-title":"Nature"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1186\/s12885-022-09756-1","article-title":"The clinicopathological and prognostic value of CXCR4 expression in patients with lung cancer: a meta-analysis","volume":"22","author":"Qiu","year":"2022","journal-title":"BMC Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1210\/me.2002-0438","article-title":"Stromal cell-derived factor 1, a novel target of estrogen receptor action, mediates the mitogenic effects of estradiol in ovarian and breast cancer cells","volume":"17","author":"Hall","year":"2003","journal-title":"Mol Endocrinol"},{"key":"B31","article-title":"Use of the stromal cell-derived factor-1\/CXCR4 pathway in prostate cancer metastasis to bone","volume":"62","author":"Taichman","year":"2002","journal-title":"Cancer Res"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1111\/his.12321","article-title":"The association of CXCR4 expression with prognosis and clinicopathological indicators in colorectal carcinoma patients: A meta-analysis","volume":"64","author":"Lv","year":"2014","journal-title":"Histopathology"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-05-1940","article-title":"Human melanoma metastases express functional CXCR4","volume":"12","author":"Scala","year":"2006","journal-title":"Clin Cancer Res"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.8.4747","article-title":"A possible role for CXCR4 and its ligand, the CXC chemokine stromal cell-derived factor-1, in the development of bone marrow metastases in neuroblastoma","volume":"167","author":"Geminder","year":"2001","journal-title":"J Immunol"},{"key":"B35","article-title":"Molecular targets in metastasis: Lessons from genomic approaches","volume":"4","author":"Fingleton","year":"2007","journal-title":"Cancer Genomics Proteomics"},{"key":"B36","first-page":"139","article-title":"Biomarker profile in breast carcinomas presenting with bone metastasis","volume":"3","author":"Bohn","year":"2010","journal-title":"Int J Clin Exp Pathol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1007\/s10585-007-9133-3","article-title":"Inhibition of the CXCR4\/CXCL12 chemokine pathway reduces the development of murine pulmonary metastases","volume":"25","author":"Kim","year":"2008","journal-title":"Clin Exp Metastasis"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1002\/pros.21008","article-title":"Effects of CXCR4 antagonist CTCE-9908 on prostate tumor growth","volume":"69","author":"Porvasnik","year":"2009","journal-title":"Prostate"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2005.02.034","article-title":"Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1\/CXCL12 secretion","volume":"121","author":"Orimo","year":"2005","journal-title":"Cell"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.05.182","article-title":"CXCR4\/CXCL12 axis promotes VEGF-mediated tumor angiogenesis through Akt signaling pathway","volume":"359","author":"Liang","year":"2007","journal-title":"Biochem Biophys Res Commun"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.6.3423","article-title":"Persistent induction of the chemokine receptor CXCR4 by TGF-beta 1 on synovial T cells contributes to their accumulation within the rheumatoid synovium","volume":"165","author":"Buckley","year":"2000","journal-title":"J Immunol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/labinvest.3700482","article-title":"Hypoxia-inducible factor 1 and VEGF upregulate CXCR4 in glioblastoma: implications for angiogenesis and glioma cell invasion","volume":"86","author":"Zagzag","year":"2006","journal-title":"Lab Invest"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)65365-5","article-title":"Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha","volume":"154","author":"Salcedo","year":"1999","journal-title":"Am J Pathol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.70.1.113","article-title":"Chemokine receptors in human basophils: inducible expression of functional CXCR4","volume":"70","author":"Iikura","year":"2001","journal-title":"J Leukoc Biol"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1189\/jlb.71.4.711","article-title":"Cytokine-mediated regulation of CXCR4 expression in human neutrophils","volume":"71","author":"Nagase","year":"2002","journal-title":"J Leukoc Biol"},{"key":"B46","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1186\/s13578-019-0315-x","article-title":"CXCR4 knockdown prevents inflammatory cytokine expression in macrophages by suppressing activation of MAPK and NF-\u03baB signaling pathways","volume":"9","author":"Tian","year":"2019","journal-title":"Cell Biosci"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0b013e32831ac557","article-title":"WHIM syndrome: Congenital immune deficiency disease","volume":"16","author":"Kawai","year":"2009","journal-title":"Curr Opin Hematol"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1038\/ng1149","article-title":"Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease","volume":"34","author":"Hernandez","year":"2003","journal-title":"Nat Genet"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2018.10.003","article-title":"Congenital neutropenia and primary immunodeficiency diseases","volume":"133","author":"Spoor","year":"2019","journal-title":"Crit Rev Oncol Hematol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"596","DOI":"10.1097\/ACI.0000000000000014","article-title":"Pathogenic mechanisms and clinical implications of congenital neutropenia syndromes","volume":"13","author":"Hauck","year":"2013","journal-title":"Curr Opin Allergy Clin Immunol"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1030-8","article-title":"Cerebellar involvement in warts Hypogammaglobulinemia immunodeficiency myelokathexis patients: neuroimaging and clinical findings","volume":"14","author":"Galli","year":"2019","journal-title":"Orphanet J Rare Dis"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1002\/(ISSN)1096-8652","article-title":"Dizygotic twin sisters with myelokathexis: mechanism of its neutropenia - PubMed","volume":"62","author":"Taniuchi","year":"1999","journal-title":"Am J Hematol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2012.05.058","article-title":"Tetralogy of fallot is an uncommon manifestation of warts, hypogammaglobulinemia, infections, and myelokathexis syndrome","volume":"161","author":"Badolato","year":"2012","journal-title":"J Pediatr"},{"key":"B54","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1186\/1750-1172-7-71","article-title":"Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry","volume":"7","author":"Beaussant Cohen","year":"2012","journal-title":"Orphanet J Rare Dis"},{"key":"B55","doi-asserted-by":"publisher","first-page":"2058","DOI":"10.1038\/s41467-023-37791-4","article-title":"WHIM Syndrome-linked CXCR4 mutations drive osteoporosis","volume":"14","author":"Anginot","year":"2023","journal-title":"Nat Commun"},{"key":"B56","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-10-461830","article-title":"The CXCR4 mutations in WHIM syndrome impair the stability of the T-cell immunologic synapse","volume":"122","author":"Kallikourdis","year":"2013","journal-title":"Blood"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.01068","article-title":"CXCL12 mediates aberrant costimulation of B lymphocytes in warts, hypogammaglobulinemia, infections, myelokathexis immunodeficiency","volume":"8","author":"Roselli","year":"2017","journal-title":"Front Immunol"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2962","article-title":"Rare and low-frequency coding variants in CXCR2 and other genes are associated with hematological traits","volume":"46","author":"Auer","year":"2014","journal-title":"Nat Genet"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2021.279254","article-title":"Biallelic CXCR2 loss-of-function mutations define a distinct congenital neutropenia entity","volume":"107","author":"Marin-Esteban","year":"2022","journal-title":"Haematologica"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020006675","article-title":"CXCR4 signaling controls dendritic cell location and activation at steady state and in inflammation","volume":"137","author":"Gallego","year":"2021","journal-title":"Blood"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaip.2019.01.045","article-title":"Long-term outcome of WHIM syndrome in 18 patients: high risk of lung disease and HPV-related Malignancies","volume":"7","author":"Dotta","year":"2019","journal-title":"J Allergy Clin Immunol Pract"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-022-01312-7","article-title":"Disease progression of WHIM syndrome in an international cohort of 66 pediatric and adult patients","volume":"42","author":"Geier","year":"2022","journal-title":"J Clin Immunol"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.13940","article-title":"Periodontal disease in patients with WHIM syndrome","volume":"51","author":"Brenchley","year":"2024","journal-title":"J Clin Periodontol"},{"key":"B64","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1038\/s41435-022-00181-9","article-title":"Genotype\u2013phenotype correlations in WHIM syndrome: a systematic characterization of CXCR4 WHIM variants","volume":"23","author":"Zmajkovicova","year":"2022","journal-title":"Genes Immun"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1111\/eci.12949","article-title":"CXCR4, the master regulator of neutrophil trafficking in homeostasis and disease","volume":"48","author":"De Filippo","year":"2018","journal-title":"Eur J Clin Invest"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-09-177287","article-title":"CXCR4 is a key regulator of neutrophil release from the bone marrow under basal and stress granulopoiesis conditions","volume":"113","author":"Eash","year":"2009","journal-title":"Blood"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-7613(03)00263-2","article-title":"Chemokines acting via CXCR2 and CXCR4 control the release of neutrophils from the bone marrow and their return following senescence","volume":"19","author":"Martin","year":"2003","journal-title":"Immunity"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-10-3638","article-title":"Role of the CXCR4\/SDF-1 chemokine axis in circulating neutrophil homeostasis","volume":"104","author":"Suratt","year":"2004","journal-title":"Blood"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.2217\/imt-2017-0027","article-title":"Rare transformation to double hit lymphoma in Waldenstrom\u2019s macroglobulinemia","volume":"9","author":"Okolo","year":"2017","journal-title":"Immunotherapy"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1097\/MOH.0000000000000254","article-title":"Oncogenic Notch signaling in T-cell and B-cell lymphoproliferative disorders","volume":"23","author":"Chiang","year":"2016","journal-title":"Curr Opin Hematol"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-09-527226","article-title":"A phase 1 clinical trial of long-term, low-dose treatment of WHIM syndrome with the CXCR4 antagonist plerixafor","volume":"123","author":"McDermott","year":"2014","journal-title":"Blood"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1172\/JCI164918","article-title":"A phase III randomized crossover trial of plerixafor versus G-CSF for treatment of WHIM syndrome","volume":"133","author":"McDermott","year":"2023","journal-title":"J Clin Invest"},{"key":"B73","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2023022658","article-title":"Phase 3 randomized trial of mavorixafor, CXCR4 antagonist, in WHIM syndrome","author":"Badolato","year":"2024","journal-title":"Blood"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.014","article-title":"Chromothriptic cure of WHIM syndrome","volume":"160","author":"McDermott","year":"2015","journal-title":"Cell"},{"key":"B75","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1182\/blood.2022019142","article-title":"CRISPR\/Cas9-mediated Cxcr4 disease allele inactivation for gene therapy in a mouse model of WHIM syndrome","volume":"142","author":"Gao","year":"2023","journal-title":"Blood"},{"key":"B76","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-09-601807","article-title":"Filamin A interaction with the CXCR4 third intracellular loop regulates endocytosis and signaling of WT and WHIM-like receptors","volume":"125","author":"G\u00f3mez-Mout\u00f3n","year":"2015","journal-title":"Blood"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2119483119","article-title":"Altered CXCR4 dynamics at the cell membrane impairs directed cell migration in WHIM syndrome patients","volume":"119","author":"Garc\u00eda-Cuesta","year":"2022","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B78","doi-asserted-by":"publisher","first-page":"ra60","DOI":"10.1126\/SCISIGNAL.2002221","article-title":"A synthetic biology approach reveals a CXCR4-G13-rho signaling axis driving transendothelial migration of metastatic breast cancer cells","volume":"4","author":"Yagi","year":"2011","journal-title":"Sci Signal"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1894","DOI":"10.1038\/s41598-023-28531-1","article-title":"Simultaneous activation of CXC chemokine receptor 4 and histamine receptor H1 enhances calcium signaling and cancer cell migration","volume":"13","author":"Park","year":"2023","journal-title":"Sci Rep"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00424-08","article-title":"Induction of the Galpha(q) signaling cascade by the human immunodeficiency virus envelope is required for virus entry","volume":"82","author":"Harmon","year":"2008","journal-title":"J Virol"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2006.11.002","article-title":"Regulation of CXCR4 signaling","volume":"1768","author":"Busillo","year":"2007","journal-title":"Biochim Biophys Acta Biomembr"},{"key":"B82","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.139.3.651","article-title":"Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4","volume":"139","author":"Signoret","year":"1997","journal-title":"J Cell Biol"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.43.31076","article-title":"Trafficking of the HIV coreceptor CXCR4. Role of arrestins and identification of residues in the c-terminal tail that mediate receptor internalization","volume":"274","author":"Orsini","year":"1999","journal-title":"J Biol Chem"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.C100527200","article-title":"Agonist-promoted ubiquitination of the G protein-coupled receptor CXCR4 mediates lysosomal sorting","volume":"276","author":"Marchese","year":"2001","journal-title":"J Biol Chem"},{"key":"B85","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.4.2479","article-title":"beta-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4","volume":"275","author":"Cheng","year":"2000","journal-title":"J Biol Chem"},{"key":"B86","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1091\/mbc.e05-05-0399","article-title":"G protein-coupled receptor kinase 2 negatively regulates chemokine signaling at a level downstream from G protein subunits","volume":"17","author":"Jim\u00e9nez-Sainz","year":"2006","journal-title":"Mol Biol Cell"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33187","article-title":"Leukocyte analysis from WHIM syndrome patients reveals a pivotal role for GRK3 in CXCR4 signaling","volume":"118","author":"Balabanian","year":"2008","journal-title":"J Clin Invest"},{"key":"B88","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.112198299","article-title":"Defective lymphocyte chemotaxis in beta-arrestin2- and GRK6-deficient mice","volume":"99","author":"Fong","year":"2002","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.1034\/J.1600-0854.2003.00079.X","article-title":"Endocytosis of the viral chemokine receptor US28 does not require beta-arrestins but is dependent on the clathrin-mediated pathway","volume":"4","author":"Fraile-Ramos","year":"2003","journal-title":"Traffic"},{"key":"B90","doi-asserted-by":"publisher","first-page":"jcs236190","DOI":"10.1242\/JCS.236190","article-title":"Rat cytomegalovirus-encoded \u03b3-chemokine vXCL1 is a highly adapted, species-specific agonist for rat XCR1-positive dendritic cells","volume":"133","author":"Bauer","year":"2019","journal-title":"J Cell Sci"},{"key":"B91","doi-asserted-by":"publisher","DOI":"10.1111\/nyas.14263","article-title":"Arrestin-independent constitutive endocytosis of GPR125\/ADGRA3","volume":"1456","author":"Spiess","year":"2019","journal-title":"Ann N Y Acad Sci"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.1124\/pr.116.013367","article-title":"The diverse roles of arrestin scaffolds in g protein\u2013coupled receptor signaling","volume":"69","author":"Peterson","year":"2017","journal-title":"Pharmacol Rev"},{"key":"B93","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.055806","article-title":"\u03b2-arrestins scaffold cofilin with chronophin to direct localized actin filament severing and membrane protrusions downstream of protease-activated receptor-2","volume":"285","author":"Zoudilova","year":"2010","journal-title":"J Biol Chem"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.1124\/mol.111.072470","article-title":"\u03b2-arrestin-dependent actin reorganization: Bringing the right players together at the leading edge","volume":"80","author":"Min","year":"2011","journal-title":"Mol Pharmacol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.06.010","article-title":"Life at the leading edge","volume":"145","author":"Ridley","year":"2011","journal-title":"Cell"},{"key":"B96","doi-asserted-by":"publisher","first-page":"102351","DOI":"10.1016\/j.jbc.2022.102351","article-title":"G protein-coupled receptor kinase phosphorylation of distal C-tail sites specifies \u03b2arrestin1-mediated signaling by chemokine receptor CXCR4","volume":"298","author":"Zhuo","year":"2022","journal-title":"J Biol Chem"},{"key":"B97","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3390\/ijms21165696","article-title":"Aberrant CXCR4 signaling at crossroad of WHIM syndrome and Waldenstrom\u2019s macroglobulinemia","volume":"21","author":"Milanesi","year":"2020","journal-title":"Int J Mol Sci"},{"key":"B98","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1182\/blood-2007-07-102103","article-title":"CXCR4 dimerization and 2-arrestin mediated signaling account for the enhanced chemotaxis to CXCL12 in WHIM syndrome","volume":"112","author":"Lagane","year":"2008","journal-title":"Blood"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-06-2289","article-title":"WHIM syndromes with different genetic anomalies are accounted for by impaired CXCR4 desensitization to CXCL12","volume":"105","author":"Balabanian","year":"2005","journal-title":"Blood"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-01-403378","article-title":"Proper desensitization of CXCR4 is required for lymphocyte development and peripheral compartmentalization in mice","volume":"119","author":"Balabanian","year":"2012","journal-title":"Blood"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.1007\/s10875-019-00665-w","article-title":"WHIM syndrome: from pathogenesis towards personalized medicine and cure","volume":"39","author":"Heusinkveld","year":"2019","journal-title":"J Clin Immunol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008102","article-title":"Impaired recruitment of Grk6 and beta-Arrestin 2 causes delayed internalization and desensitization of a WHIM syndrome-associated CXCR4 mutant receptor","volume":"4","author":"McCormick","year":"2009","journal-title":"PloS One"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01262","article-title":"Enhanced bone marrow homing of natural killer cells following mRNA transfection with gain-of-function variant CXCR4R334X","volume":"10","author":"Levy","year":"2019","journal-title":"Front Immunol"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20160806","article-title":"Lymphoid differentiation of hematopoietic stem cells requires efficient Cxcr4 desensitization","volume":"214","author":"Freitas","year":"2017","journal-title":"J Exp Med"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2014.187","article-title":"The WHIM-like CXCR4(S338X) somatic mutation activates AKT and ERK, and promotes resistance to ibrutinib and other agents used in the treatment of Waldenstrom\u2019s Macroglobulinemia","volume":"29","author":"Cao","year":"2015","journal-title":"Leukemia"},{"key":"B106","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-12-395608","article-title":"WHIM syndrome caused by a single amino acid substitution in the carboxy-tail of chemokine receptor CXCR4","volume":"120","author":"Liu","year":"2012","journal-title":"Blood"},{"key":"B107","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0064975","article-title":"Hierarchical organization of multi-site phosphorylation at the CXCR4 C terminus","volume":"8","author":"Mueller","year":"2013","journal-title":"PloS One"},{"key":"B108","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/s12860-021-00347-9","article-title":"The negative charge of the 343 site is essential for maintaining physiological functions of CXCR4","volume":"22","author":"Wang","year":"2021","journal-title":"BMC Mol Cell Biol"},{"key":"B109","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.gendis.2019.09.015","article-title":"An updated review on activated PI3 kinase delta syndrome (APDS)","volume":"7","author":"Singh","year":"2019","journal-title":"Genes Dis"},{"key":"B110","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.145688","article-title":"Reduced G protein signaling despite impaired internalization and \u03b2-arrestin recruitment in patients carrying a CXCR4Leu317fsX3 mutation causing WHIM syndrome","volume":"8","author":"Kumar","year":"2023","journal-title":"JCI Insight"},{"key":"B111","doi-asserted-by":"publisher","first-page":"101551","DOI":"10.1016\/j.jbc.2021.101551","article-title":"Characterization of a new WHIM syndrome mutant reveals mechanistic differences in regulation of the chemokine receptor CXCR4","volume":"298","author":"Luo","year":"2022","journal-title":"J Biol Chem"},{"key":"B112","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023011875","article-title":"A novel transmembrane CXCR4 variant that expands the WHIM genotype-phenotype paradigm","author":"Zmajkovicova","year":"2024","journal-title":"Blood Adv"},{"key":"B113","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.0611448104","article-title":"A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein","volume":"104","author":"Whorton","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B114","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)79672-9","article-title":"A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled \u03b2-adrenergic receptor","volume":"255","author":"De Lean","year":"1980","journal-title":"J Biol Chem"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.2174\/092986712799320619","article-title":"Ensemble of G protein-coupled receptor active states","volume":"19","author":"Park","year":"2012","journal-title":"Curr Med Chem"},{"key":"B116","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M703346200","article-title":"Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer","volume":"283","author":"Whorton","year":"2008","journal-title":"J Biol Chem"},{"key":"B117","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1110499108","article-title":"Activation mechanism of the \u03b2 2-adrenergic receptor","volume":"108","author":"Dror","year":"2011","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B118","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.01.008","article-title":"The dynamic process of \u03b22-adrenergic receptor activation","volume":"152","author":"Nygaard","year":"2013","journal-title":"Cell"},{"key":"B119","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.04.043","article-title":"Structural insights into the dynamic process of \u03b22-adrenergic receptor signaling","volume":"161","author":"Manglik","year":"2015","journal-title":"Cell"},{"key":"B120","doi-asserted-by":"publisher","first-page":"6996","DOI":"10.1093\/emboj\/16.23.6996","article-title":"Solution structure and basis for functional activity of stromal cell-derived factor-1; dissociation of CXCR4 activation from binding and inhibition of HIV-1","volume":"16","author":"Crump","year":"1997","journal-title":"EMBO J"},{"key":"B121","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0165-2478(01)00228-0","article-title":"Pharmacological evidence for complex and multiple site interaction of CXCR4 with SDF-1\u03b1: Implications for development of selective CXCR4 antagonists","volume":"78","author":"Gupta","year":"2001","journal-title":"Immunol Lett"},{"key":"B122","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1601278113","article-title":"Signal transmission through the CXC chemokine receptor 4 (CXCR4) transmembrane helices","volume":"113","author":"Wescott","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"B123","doi-asserted-by":"publisher","DOI":"10.1016\/j.sbi.2011.06.002","article-title":"Structural insights into agonist-induced activation of G-protein-coupled receptors","volume":"21","author":"Deupi","year":"2011","journal-title":"Curr Opin Struct Biol"},{"key":"B124","doi-asserted-by":"publisher","DOI":"10.1124\/mol.61.5.1025","article-title":"Mutagenesis and modelling of the alpha(1b)-adrenergic receptor highlight the role of the helix 3\/helix 6 interface in receptor activation","volume":"61","author":"Greasley","year":"2002","journal-title":"Mol Pharmacol"},{"key":"B125","doi-asserted-by":"publisher","first-page":"e42765","DOI":"10.1371\/journal.pone.0042765","article-title":"Leu128(3.43) (l128) and Val247(6.40) (V247) of CXCR1 are critical amino acid residues for g protein coupling and receptor activation","volume":"7","author":"Han","year":"2012","journal-title":"PloS One"},{"key":"B126","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0811437106","article-title":"The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex","volume":"106","author":"Xiao","year":"2009","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.1038\/nature18324","article-title":"Allosteric coupling from G protein to the agonist-binding pocket in GPCRs","volume":"535","author":"Devree","year":"2016","journal-title":"Nature"},{"key":"B128","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1038\/nature22354","article-title":"Single-molecule analysis of ligand efficacy in \u03b22AR-G-protein activation","volume":"547","author":"Gregorio","year":"2017","journal-title":"Nature"},{"key":"B129","doi-asserted-by":"publisher","first-page":"6826","DOI":"10.1038\/s41467-022-34382-7","article-title":"Computationally designed GPCR quaternary structures bias signaling pathway activation","volume":"13","author":"Paradis","year":"2022","journal-title":"Nat Commun"},{"key":"B130","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1016\/j.ceb.2013.11.008","article-title":"Single-molecule imaging revealed dynamic GPCR dimerization","volume":"27","author":"Kasai","year":"2014","journal-title":"Curr Opin Cell Biol"},{"key":"B131","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.05.006","article-title":"Asymmetry of GPCR oligomers supports their functional relevance","volume":"32","author":"Maurice","year":"2011","journal-title":"Trends Pharmacol Sci"},{"key":"B132","doi-asserted-by":"publisher","DOI":"10.1016\/bs.ircmb.2018.02.005","article-title":"The dynamics of GPCR oligomerization and their functional consequences","volume":"338","author":"Sleno","year":"2018","journal-title":"Int Rev Cell Mol Biol"},{"key":"B133","article-title":"Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine","volume":"301","author":"Qin","year":"2014","journal-title":"Sci (1979)"},{"key":"B134","doi-asserted-by":"publisher","DOI":"10.1126\/science.1150577","article-title":"High-resolution crystal structure of an engineered human \u03b22-adrenergic G protein-coupled receptor","volume":"318","author":"Cherezov","year":"2007","journal-title":"Sci (1979)"},{"key":"B135","doi-asserted-by":"publisher","first-page":"897","DOI":"10.1016\/j.str.2008.05.001","article-title":"A specific cholesterol binding site is established by the 2.8 \u00c5 Structure of the human \u03b22-adrenergic receptor","volume":"16","author":"Hanson","year":"2008","journal-title":"Structure"},{"key":"B136","doi-asserted-by":"publisher","DOI":"10.1126\/science.1164772","article-title":"The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist","volume":"322","author":"Jaakola","year":"2008","journal-title":"Science"},{"key":"B137","doi-asserted-by":"publisher","DOI":"10.1007\/s10822-006-9064-0","article-title":"Inactive and active states and supramolecular organization of GPCRs: insights from computational modeling","volume":"20","author":"Fanelli","year":"2006","journal-title":"J Comput Aided Mol Des"},{"key":"B138","doi-asserted-by":"publisher","DOI":"10.1042\/BST0350749","article-title":"Computational studies of family A and family B GPCRs","volume":"35","author":"Vohra","year":"2007","journal-title":"Biochem Soc Trans"},{"key":"B139","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.8.3779-3790.2001","article-title":"CCR5, CXCR4, and CD4 are clustered and closely apposed on microvilli of human macrophages and T cells","volume":"75","author":"Singer","year":"2001","journal-title":"J Virol"},{"key":"B140","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.10.2497","article-title":"Chemokine receptor homo- or heterodimerization activates distinct signaling pathways","volume":"20","author":"Mellado","year":"2001","journal-title":"EMBO J"},{"key":"B141","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/j.1476-5381.2009.00169.x","article-title":"G protein-coupled receptor hetero-dimerization: contribution to pharmacology and function","volume":"158","author":"Milligan","year":"2009","journal-title":"Br J Pharmacol"},{"key":"B142","doi-asserted-by":"crossref","DOI":"10.1096\/fasebj.13.13.1699","article-title":"The chemokine SDF-l\u03b1 triggers CXCR4 receptor dimerization and activates the JAK\/STAT pathway","volume":"13","author":"Vila-Coro","year":"1999","journal-title":"FASEB J"},{"key":"B143","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210140200","article-title":"Ligand-independent dimerization of CXCR4, a principal HIV-1 coreceptor","volume":"278","author":"Babcock","year":"2003","journal-title":"J Biol Chem"},{"key":"B144","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200737630","article-title":"Ligand stabilization of CXCR4\/\u03b4-opioid receptor heterodimers reveals a mechanism for immune response regulation","volume":"38","author":"Pello","year":"2008","journal-title":"Eur J Immunol"},{"key":"B145","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1322887111","article-title":"CCR5\/CD4\/CXCR4 oligomerization prevents HIV-1 gp120IIIB binding to the cell surface","volume":"111","author":"Martinez-Munoz","year":"2014","journal-title":"Proc Natl Acad Sci"},{"key":"B146","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705302200","article-title":"Allosteric transinhibition by specific antagonists in CCR2\/CXCR4 heterodimers","volume":"282","author":"Sohy","year":"2007","journal-title":"J Biol Chem"},{"key":"B147","doi-asserted-by":"publisher","DOI":"10.1073\/PNAS.0702229104","article-title":"Disrupted cardiac development but normal hematopoiesis in mice deficient in the second CXCL12\/SDF-1 receptor, CXCR7","volume":"104","author":"Sierro","year":"2007","journal-title":"Proc Natl Acad Sci U.S.A"},{"key":"B148","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.925559","article-title":"Sphingomyelin depletion inhibits CXCR4 dynamics and CXCL12-mediated directed cell migration in human T cells","volume":"13","author":"Gardeta","year":"2022","journal-title":"Front Immunol"},{"key":"B149","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.molcel.2018.02.034","article-title":"Separating actin-dependent chemokine receptor nanoclustering from dimerization indicates a role for clustering in CXCR4 signaling and function","volume":"70","author":"Mart\u00ednez-Mu\u00f1oz","year":"2018","journal-title":"Mol Cell"},{"key":"B150","doi-asserted-by":"publisher","DOI":"10.3389\/FIMMU.2020.550824","article-title":"\u03b2-arrestin1 and \u03b2-arrestin2 are required to support the\u00a0activity of the CXCL12\/HMGB1 heterocomplex on CXCR4","volume":"11","author":"D\u2019Agostino","year":"2020","journal-title":"Front Immunol"},{"key":"B151","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M606877200","article-title":"Helix 8 of the viral chemokine receptor ORF74 directs chemokine binding","volume":"281","author":"Verzijl","year":"2006","journal-title":"J Biol Chem"},{"key":"B152","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03819-2","article-title":"Highly accurate protein structure prediction with AlphaFold","volume":"596","author":"Jumper","year":"2021","journal-title":"Nature"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1406532\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T04:43:25Z","timestamp":1720154605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2024.1406532\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,5]]},"references-count":152,"alternative-id":["10.3389\/fimmu.2024.1406532"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2024.1406532","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,7,5]]},"article-number":"1406532"}}