{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T02:46:15Z","timestamp":1794278775576,"version":"4.9.0"},"reference-count":105,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T00:00:00Z","timestamp":1748822400000},"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>Interleukin (IL)-16 is expressed mostly by the cells of the human immune system. Upon cell activation IL-16 is cleaved, forming two functional proteins, one regulating cell cycle and the other acting as chemoattractant for the cells carrying CD4 or CD9. Increased levels of IL-16 are found in the circulation and at the sites of inflammation, infection and cancer. Polymorphisms in the IL-16 gene have been coupled to several of these conditions and high IL-16 has been suggested as a disease biomarker. Using unbiased proteomic approach we and others independently identified IL-16 as a biomarker of severe lupus nephritis, and top-expressed cytokine in skin lesions of lupus erythematosus. Recently, an unbiased investigation identified IL-16 as a top candidate for novel drug target. Blockade of IL-16 showed positive therapeutic effects in several animal models of human disease with low rate of side effects. Importantly, it has been recently demonstrated that IL-16 can be released during pyroptosis, a proinflammatory cell death pathway. This finding disclosed a novel role of IL-16 as a mediator of response to the proinflammatory cell death and may explain why IL-16 is detected at the sites of inflammation, infection or cancer. In this review we cover the knowledge on the biology of IL-16 and its importance in human diseases. We aim that this manuscript will be informative and prove benefits of possible therapeutic blockade of IL-16.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1524026","type":"journal-article","created":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:22:34Z","timestamp":1748841754000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":25,"title":["Role of interleukin-16 in human diseases: a novel potential therapeutic target"],"prefix":"10.3389","volume":"16","author":[{"given":"Timothy B.","family":"Niewold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia S.","family":"Lehman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iva","family":"Gunnarsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Meves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vilija","family":"Oke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,6,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1159\/000015224","article-title":"Assignment of human interleukin 16 (IL16) to chromosome 15q26.3 by radiation hybrid mapping","volume":"84","author":"Kim","year":"1999","journal-title":"Cytogenet Cell Genet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.19-18-07770.1999","article-title":"Neuronal interleukin-16 (NIL-16): A dual function PDZ domain protein","volume":"19","author":"Kurschner","year":"1999","journal-title":"J Neurosci"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.67.6.757","article-title":"Interleukin-16","volume":"67","author":"Cruikshank","year":"2000","journal-title":"J Leukoc Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/s1357-2725(97)00053-8","article-title":"Interleukin-16","volume":"29","author":"Center","year":"1997","journal-title":"Int J Biochem Cell Biol"},{"key":"B5","article-title":"Activation of caspase-3 by interferon alpha causes interleukin-16 secretion but fails to modulate activation induced cell death","volume":"12","author":"Ludwiczek","year":"2001","journal-title":"Eur Cytokine Netw"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.4.1827","article-title":"Identification of domains in IL-16 critical for biological activity","volume":"163","author":"Nicoll","year":"1999","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1654","article-title":"Nuclear pro-IL-16 regulation of T cell proliferation: p27KIP1-dependent G0\/G1 arrest mediated by inhibition of skp2 transcription","volume":"172","author":"Center","year":"2004","journal-title":"J Immunol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/1376","article-title":"Structure of interleukin 16 resembles a PDZ domain with an occluded peptide binding site","volume":"5","author":"M\u00fchlhahn","year":"1998","journal-title":"Nat Struct Biol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1080\/08977190410001704679","article-title":"The effect of interleukin-16 and its precursor on T lymphocyte activation and growth","volume":"22","author":"Wilson","year":"2004","journal-title":"Growth Factors Chur Switz"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.162.3.1287","article-title":"Processing and release of IL-16 from CD4+ but not CD8+ T cells is activation dependent","volume":"162","author":"Wu","year":"1999","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/eji.200324598","article-title":"Identification of pro-interleukin 16 as a novel target of MAP kinases in activated T lymphocytes","volume":"34","author":"Laurence","year":"2004","journal-title":"Eur J Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.5.2738","article-title":"Pro-IL-16 regulation in activated murine CD4+ Lymphocytes","volume":"174","author":"Ren","year":"2005","journal-title":"J Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.2.1144","article-title":"Processing and activation of pro-interleukin-16 by caspase-3*","volume":"273","author":"Zhang","year":"1998","journal-title":"J Biol Chem"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.164.7.3806","article-title":"Cultured human fibroblasts express constitutive IL-16 mRNA: cytokine induction of active IL-16 protein synthesis through a caspase-3-dependent mechanism","volume":"164","author":"Sciaky","year":"2000","journal-title":"J Immunol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3109\/15476911003649346","article-title":"IL-16 effects on A549 lung epithelial cells: Dependence on CD9 as an IL-16 receptor","volume":"7","author":"Yadav","year":"2010","journal-title":"J Immunotoxicol"},{"key":"B16","unstructured":"Human Protein Atlas"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.7.2566","article-title":"Human eosinophils elaborate the lymphocyte chemoattractants. IL-16 (lymphocyte chemoattractant factor) and RANTES","volume":"156","author":"Lim","year":"1996","journal-title":"J Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.157.12.5240","article-title":"IL-16 inhibition of CD3-dependent lymphocyte activation and proliferation","volume":"157","author":"Cruikshank","year":"1996","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.159.6.2904","article-title":"Human mast cells produce the CD4+ T lymphocyte chemoattractant factor, IL-16","volume":"159","author":"Rumsaeng","year":"1997","journal-title":"J Immunol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.6.3232","article-title":"A role for IL-16 in the cross-talk between dendritic cells and T cells","volume":"163","author":"Kaser","year":"1999","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B21","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1186\/s12974-015-0292-x","article-title":"Role of IL-16 in CD4+ T cell-mediated regulation of relapsing multiple sclerosis","volume":"12","author":"Skundric","year":"2015","journal-title":"J Neuroinflamm"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.156.1.310","article-title":"Secretion of IL-16 (lymphocyte chemoattractant factor) from serotonin-stimulated CD8+ T cells in vitro","volume":"156","author":"Laberge","year":"1996","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.163.6.3123","article-title":"Reciprocal desensitization of CCR5 and CD4 is mediated by IL-16 and macrophage-inflammatory protein-1\u03b2, respectively","volume":"163","author":"Mashikian","year":"1999","journal-title":"J Immunol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.10.4965","article-title":"Cutting edge: IL-16\/CD4 preferentially induces th1 cell migration: requirement of CCR5","volume":"171","author":"Lynch","year":"2003","journal-title":"J Immunol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-03-1312","article-title":"Human and mouse mast cells use the tetraspanin CD9 as an alternate interleukin-16 receptor","volume":"107","author":"Qi","year":"2005","journal-title":"Blood"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2001.01328.x","article-title":"Interleukin-16 supports the migration of langerhans cells, partly in a CD4-independent way","volume":"116","author":"Stoitzner","year":"2001","journal-title":"J Invest Dermatol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1002\/(sici)1521-4141(199809)28:09<2661::aid-immu2661>3.0.co;2-n","article-title":"Interleukin-16, produced by synovial fibroblasts, mediates chemoattraction for CD4+ T lymphocytes in rheumatoid arthritis","volume":"28","author":"Franz","year":"1998","journal-title":"Eur J Immunol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.2000.00959.x","article-title":"Human B-cell lines constitutively express and secrete interleukin-16","volume":"99","author":"Sharma","year":"2000","journal-title":"Immunology"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2024.110115","article-title":"Enhanced interleukin-16-CD4 signaling in CD3 T cell mediates neuropathic pain via activating astrocytes in female mice","volume":"259","author":"Zhu","year":"2024","journal-title":"Neuropharmacology"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1996.0054","article-title":"IL-16- and other CD4 ligand-induced migration is dependent upon protein kinase C","volume":"168","author":"Parada","year":"1996","journal-title":"Cell Immunol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.274.33.23387","article-title":"Identification of a CD4 domain required for interleukin-16 binding and lymphocyte activation*","volume":"274","author":"Liu","year":"1999","journal-title":"J Biol Chem"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.4.2337","article-title":"Chemokine receptor CXCR3 desensitization by IL-16\/CD4 signaling is dependent on CCR5 and intact membrane cholesterol","volume":"176","author":"Rahangdale","year":"2006","journal-title":"J Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6356","article-title":"Desensitization of CXC chemokine receptor 4, mediated by IL-16\/CD4, is independent of p56lck enzymatic activity","volume":"165","author":"Drenth","year":"2000","journal-title":"J Immunol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.24441","article-title":"Regulation of cellular processes by interleukin-16 in homeostasis and cancer","volume":"229","author":"Richmond","year":"2014","journal-title":"J Cell Physiol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"493","DOI":"10.7150\/ijbs.29404","article-title":"CD9 regulates keratinocyte migration by negatively modulating the sheddase activity of ADAM17","volume":"15","author":"Liu","year":"2019","journal-title":"Int J Biol Sci"},{"key":"B36","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cellimm.2005.09.003","article-title":"Regulation of nuclear Prointerleukin-16 and p27Kip1 in primary human T lymphocytes","volume":"237","author":"Wilson","year":"2005","journal-title":"Cell Immunol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1999.00693.x","article-title":"Inhibitory effect of interleukin-16 on interleukin-2 production by CD4+ T cells","volume":"96","author":"Ogasawara","year":"1999","journal-title":"Immunology"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.2147\/copd.s103758","article-title":"Interleukin-16-producing NK cells and T-cells in the blood of tobacco smokers with and without COPD","volume":"11","author":"Andersson","year":"2016","journal-title":"Int J Chronic Obstr"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.5.2474","article-title":"B lymphocyte-derived IL-16 attracts dendritic cells and th cells","volume":"165","author":"Kaser","year":"2000","journal-title":"J Immunol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"e120798","DOI":"10.1172\/jci.insight.120798","article-title":"IL-16\/miR-125a axis controls neutrophil recruitment in pristane-induced lung inflammation","volume":"3","author":"Smith","year":"2018","journal-title":"JCI Insight"},{"key":"B41","doi-asserted-by":"publisher","first-page":"15056","DOI":"10.1038\/cddiscovery.2015.56","article-title":"Secondary necrotic neutrophils release interleukin-16C and macrophage migration inhibitory factor from stores in the cytosol","volume":"1","author":"Roth","year":"2015","journal-title":"Cell Death Discov"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.12.7721","article-title":"IL-16 is constitutively present in peripheral blood monocytes and spontaneously released during apoptosis","volume":"172","author":"Elssner","year":"2004","journal-title":"J Immunol"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1038\/mi.2014.24","article-title":"Secretion of IL-16 through TNFR1 and calpain-caspase signaling contributes to MRSA pneumonia","volume":"7","author":"Ahn","year":"2014","journal-title":"Mucosal Immunol"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.167.11.6321","article-title":"Engagement of the Fc epsilon RI stimulates the production of IL-16 in Langerhans cell-like dendritic cells","volume":"167","author":"Reich","year":"2001","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1900101","article-title":"Cytokine diversity in human peripheral blood eosinophils: profound variability of IL-16","volume":"203","author":"Ma","year":"2019","journal-title":"J Immunol"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1007\/s00405-007-0300-6","article-title":"The role of interleukin-16 in eosinophilic chronic rhinosinusitis","volume":"264","author":"Lackner","year":"2007","journal-title":"Eur Arch Oto-Rhino-Laryngol"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.5.2115","article-title":"Synergistic activation of CD4+ T cells by IL-16 and IL-2","volume":"160","author":"Parada","year":"1998","journal-title":"J Immunol (Baltim Md: 1950)"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.2337\/db09-0131","article-title":"Neutralization of interleukin-16 protects nonobese diabetic mice from autoimmune type 1 diabetes by a CCL4-dependent mechanism","volume":"59","author":"Meagher","year":"2010","journal-title":"Diabetes"},{"key":"B49","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.molimm.2018.12.027","article-title":"IL-16 regulates macrophage polarization as a target gene of mir-145-3p","volume":"107","author":"Huang","year":"2019","journal-title":"Mol Immunol"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2008.0187","article-title":"IL-16 can synergize with early acting cytokines to expand ex vivo CD34 isolated from cord blood","volume":"18","author":"Rofani","year":"2009","journal-title":"Stem Cells Dev"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2004-03-0885","article-title":"Are interleukin-16 and thrombopoietin new tools for the in vitro generation of dendritic cells","volume":"104","author":"Bella","year":"2004","journal-title":"Blood"},{"key":"B52","doi-asserted-by":"publisher","first-page":"595","DOI":"10.1111\/j.1365-2249.2004.02570.x","article-title":"Interleukin-16 expression and release in bullous pemphigoid","volume":"137","author":"Frezzolini","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1515\/cclm-2017-1047","article-title":"IL8 and IL16 levels indicate serum and plasma quality","volume":"56","author":"Kofanova","year":"2018","journal-title":"Clin Chem Lab Med (CCLM)"},{"key":"B54","doi-asserted-by":"publisher","DOI":"10.1038\/s42255-020-00287-2","article-title":"Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals","volume":"2","author":"Folkersen","year":"2020","journal-title":"Nat Metab"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e8396","DOI":"10.1097\/md.0000000000008396","article-title":"Elevated plasma levels of interleukin-16 in patients with acute myocardial infarction","volume":"96","author":"Schernthaner","year":"2017","journal-title":"Medicine"},{"key":"B56","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.cyto.2015.12.002","article-title":"Serum proteomic analysis identifies interleukin 16 as a biomarker for clinical response during early treatment of rheumatoid arthritis","volume":"78","author":"Murota","year":"2016","journal-title":"Cytokine"},{"key":"B57","doi-asserted-by":"publisher","first-page":"e0165577","DOI":"10.1371\/journal.pone.0165577","article-title":"Assessment of interleukin 16 serum levels and skin expression in psoriasis patients in correlation with clinical severity of the disease","volume":"11","author":"Purzycka-Bohdan","year":"2016","journal-title":"PloS One"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.1136\/gut.48.3.326","article-title":"Increased expression of IL-16 in inflammatory bowel disease","volume":"48","author":"Seegert","year":"2001","journal-title":"Gut"},{"key":"B59","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2000.18164","article-title":"Interleukin 16 is up-regulated in Crohn\u2019s disease and participates in TNBS colitis in mice","volume":"119","author":"Keates","year":"2000","journal-title":"Gastroenterology"},{"key":"B60","doi-asserted-by":"publisher","first-page":"e000744","DOI":"10.1136\/lupus-2022-000744","article-title":"Interleukin (IL) 16: a candidate urinary biomarker for proliferative lupus nephritis","volume":"9","author":"H\u00e4yry","year":"2022","journal-title":"Lupus Sci Med"},{"key":"B61","doi-asserted-by":"publisher","first-page":"e000260","DOI":"10.1136\/lupus-2018-000260","article-title":"TNF-\u03b1 and plasma albumin as biomarkers of disease activity in systemic lupus erythematosus","volume":"5","author":"Idborg","year":"2018","journal-title":"Lupus Sci Med"},{"key":"B62","doi-asserted-by":"publisher","DOI":"10.1002\/art.42023","article-title":"Urine proteomics and renal single cell transcriptomics implicate IL-16 in lupus nephritis","volume":"74","author":"Fava","year":"2021","journal-title":"Arthritis Rheumatol"},{"key":"B63","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13075-020-02172-5","article-title":"Serum interleukin-16 significantly correlates with the Vasculitis Damage Index in antineutrophil cytoplasmic antibody-associated vasculitis","volume":"22","author":"Yoon","year":"2020","journal-title":"Arthritis Res Ther"},{"key":"B64","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1186\/s13075-022-02740-x","article-title":"A comprehensive profile of chemokines in the peripheral blood and vascular tissue of patients with Takayasu arteritis","volume":"24","author":"Kong","year":"2021","journal-title":"Arthritis Res Ther"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kez318","article-title":"IL-16 expression is increased in the skin and sera of patients with systemic sclerosis","volume":"59","author":"Kawabata","year":"2019","journal-title":"Rheumatology"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.00451","article-title":"High-dose dexamethasone alters the increase in interleukin-16 level in adult immune thrombocytopenia","volume":"10","author":"Wang","year":"2019","journal-title":"Front Immunol"},{"key":"B67","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0199","article-title":"Cytokine-induced lymphocyte chemoattraction from cultured human thyrocytes: evidence for interleukin-16 and regulated upon activation, normal T cell expressed, and secreted expression","volume":"144","author":"Gianoukakis","year":"2003","journal-title":"Endocrinology"},{"key":"B68","doi-asserted-by":"publisher","DOI":"10.15586\/aei.v50i5.592","article-title":"Investigation of serum IL-12, IL-16, and IL-17A as diagnostic biomarkers in children with cow\u2019s milk protein allergy","volume":"50","author":"Mao","year":"2022","journal-title":"Allergol Immunopath"},{"key":"B69","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2004.12.004","article-title":"Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis","volume":"83","author":"Koga","year":"2005","journal-title":"Fertil Steril"},{"key":"B70","doi-asserted-by":"publisher","DOI":"10.1016\/j.xcrm.2024.101476","article-title":"Pyroptotic T cell-derived active IL-16 has a driving function in ovarian endometriosis development","volume":"5","author":"Zhang","year":"2024","journal-title":"Cell Rep Med"},{"key":"B71","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2015.01.005","article-title":"Emerging role of IL-16 in cytokine-mediated regulation of multiple sclerosis","volume":"75","author":"Skundric","year":"2015","journal-title":"Cytokine"},{"key":"B72","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-3-13","article-title":"Production of IL-16 correlates with CD4+ Th1 inflammation and phosphorylation of axonal cytoskeleton in multiple sclerosis lesions","volume":"3","author":"Skundric","year":"2006","journal-title":"J Neuroinflamm"},{"key":"B73","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1111\/ane.12215","article-title":"Interferon \u03b2-1a reduces increased interleukin-16 levels in multiple sclerosis patients","volume":"130","author":"Nischwitz","year":"2014","journal-title":"Acta Neurol Scand"},{"key":"B74","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.20377","article-title":"Anti-IL-16 therapy reduces CD4+ T-cell infiltration and improves paralysis and histopathology of relapsing EAE","volume":"79","author":"Skundric","year":"2005","journal-title":"J Neurosci Res"},{"key":"B75","doi-asserted-by":"publisher","first-page":"327239","DOI":"10.1101\/327239","article-title":"Assessing 42 inflammatory markers in 321 control subjects and 887 major depressive disorder cases: BMI and other confounders and overall predictive ability for current depression","author":"Powell","year":"2018","journal-title":"bioRxiv"},{"key":"B76","doi-asserted-by":"publisher","first-page":"7344","DOI":"10.1038\/s41598-024-57350-1","article-title":"In major dysmood disorder, physiosomatic, chronic fatigue and fibromyalgia symptoms are driven by immune activation and increased immune-associated neurotoxicity","volume":"14","author":"Maes","year":"2024","journal-title":"Sci Rep"},{"key":"B77","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-3917221\/v1","article-title":"Hyperalgesic effect evoked by il-16 and its participation in inflammatory hypernociception in mice","author":"Gonz\u00e1lez-Rodr\u00edguez","year":"2024"},{"key":"B78","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2023.111411","article-title":"Spinal interleukin-16 mediates inflammatory pain via promoting glial activation","volume":"127","author":"Zhu","year":"2024","journal-title":"Int Immunopharmacol"},{"key":"B79","doi-asserted-by":"publisher","first-page":"e00037-17","DOI":"10.1128\/cvi.00037-17","article-title":"Cytokines are markers of the clostridium difficile-induced inflammatory response and predict disease severity","volume":"24","author":"Yu","year":"2017","journal-title":"Clin Vaccine Immunol"},{"key":"B80","doi-asserted-by":"publisher","DOI":"10.1038\/nm0697-659","article-title":"Human CD4+ cells transfected with IL-16 cDNA are resistant to HIV-1 infection: Inhibition of mRNA expression","volume":"3","author":"Zhou","year":"1997","journal-title":"Nat Med"},{"key":"B81","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12081707","article-title":"Adeno-associated virus (AAV)-delivered exosomal TAT and biTE molecule CD4-\u03b1CD3 facilitate the elimination of CD4 T cells harboring latent HIV-1","volume":"12","author":"Tang","year":"2024","journal-title":"Microorganisms"},{"key":"B82","doi-asserted-by":"publisher","first-page":"10324","DOI":"10.1038\/s41598-024-61133-z","article-title":"Multi-cohort study on cytokine and chemokine profiles in the progression of COVID-19","volume":"14","author":"Huang","year":"2024","journal-title":"Sci Rep"},{"key":"B83","doi-asserted-by":"publisher","DOI":"10.1080\/22221751.2024.2322663","article-title":"Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth","volume":"13","author":"Su","year":"2024","journal-title":"Emerg Microbes Infect"},{"key":"B84","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6616422","article-title":"Anti-interleukin-16 neutralizing antibody treatment alleviates sepsis-induced cardiac injury and dysfunction via the nuclear factor erythroid-2 related factor 2 pathway in mice","volume":"2021","author":"Zhang","year":"2021","journal-title":"Oxid Med Cell Longev"},{"key":"B85","doi-asserted-by":"publisher","first-page":"e23411","DOI":"10.5812\/jjm.23411","article-title":"A study on genetic association of interleukin-16 single nucleotide polymorphism (rs1131445) with chronic hepatitis B virus infection in Iranian patients","volume":"8","author":"Behelgardi","year":"2015","journal-title":"Jundishapur J Microbiol"},{"key":"B86","doi-asserted-by":"publisher","DOI":"10.1111\/j.1442-2042.2010.02559.x","article-title":"IL-16 polymorphism and risk of renal cell carcinoma: association in a Chinese population","volume":"17","author":"Zhu","year":"2010","journal-title":"Int J Urol: Off J Jpn Urol Assoc"},{"key":"B87","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.m008513200","article-title":"Nuclear translocation of the N-terminal prodomain of interleukin-16*","volume":"276","author":"Zhang","year":"2001","journal-title":"J Biol Chem"},{"key":"B88","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1007\/s10875-010-9464-8","article-title":"Interleukin-16 as a marker of s\u00e9zary syndrome onset and stage","volume":"31","author":"Richmond","year":"2011","journal-title":"J Clin Immunol"},{"key":"B89","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2014.919634","article-title":"CCR4 + T cell recruitment to the skin in mycosis fungoides: potential contributions by thymic stromal lymphopoietin and interleukin-16","volume":"56","author":"Tuzova","year":"2015","journal-title":"Leuk Lymphoma"},{"key":"B90","doi-asserted-by":"publisher","DOI":"10.1182\/blood.v122.21.5367.5367","article-title":"Cytokine interleukin-16 supports progression of multiple myeloma through different molecular mechanisms","volume":"122","author":"Templin","year":"2013","journal-title":"Blood"},{"key":"B91","doi-asserted-by":"publisher","first-page":"e12926","DOI":"10.1111\/sji.12926","article-title":"IL-16 processing in sentinel node regulatory T cells is a factor in bladder cancer immunity","volume":"92","author":"Krantz","year":"2020","journal-title":"Scand J Immunol"},{"key":"B92","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.188.supp.47.5","article-title":"Loss of nuclear Pro-IL-16 imparts resistance to apoptosis in CTCL T cells (47.5)","volume":"188","author":"Tuzova","year":"2012","journal-title":"J Immunol"},{"key":"B93","first-page":"12","article-title":"Interleukin 16 expression in relation to disease activity in rheumatoid arthritis","volume":"28","author":"Blaschke","year":"2001","journal-title":"J Rheumatol"},{"key":"B94","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.173.5.3564","article-title":"Synovial fibroblasts from patients with rheumatoid arthritis, like fibroblasts from graves\u2019 Disease, express high levels of IL-16 when treated with igs against insulin-like growth factor-1 receptor","volume":"173","author":"Pritchard","year":"2004","journal-title":"J Immunol"},{"key":"B95","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/37.12.1334","article-title":"Circulating interleukin-16 in systemic lupus erythematosus","volume":"37","author":"Lee","year":"1998","journal-title":"Br J Rheumatol"},{"key":"B96","doi-asserted-by":"publisher","DOI":"10.21203\/rs.3.rs-145148\/v1","article-title":"Proteome study of cutaneous lupus erythematosus (CLE) and dermatomyositis skin lesions reveals IL-16 is differentially upregulated in CLE","author":"Niewold","year":"2021"},{"key":"B97","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.2.942","article-title":"Igs from patients with graves\u2019 Disease induce the expression of T cell chemoattractants in their fibroblasts","volume":"168","author":"Pritchard","year":"2002","journal-title":"J Immunol"},{"key":"B98","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-3083.2011.02630.x","article-title":"In type 1 diabetes immunocompetent cells are defective in IL-16 secretion","volume":"75","author":"Vendrame","year":"2012","journal-title":"Scand J Immunol"},{"key":"B99","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-023-06381-z","article-title":"Neutralizing IL-16 enhances the efficacy of targeting Aurora-A therapy in colorectal cancer with high lymphocyte infiltration through restoring anti-tumor immunity","volume":"15","author":"Yang","year":"2024","journal-title":"Cell Death Dis"},{"key":"B100","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.841732","article-title":"Pyroptosis and its role in autoimmune disease: A potential therapeutic target","volume":"13","author":"You","year":"2022","journal-title":"Front Immunol"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2022.855828","article-title":"Gasdermin E: A prospective target for therapy of diseases","volume":"13","author":"Liao","year":"2022","journal-title":"Front Pharmacol"},{"key":"B102","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13143620","article-title":"Pyroptosis in cancer: friend or foe","volume":"13","author":"Lu","year":"2021","journal-title":"Cancers"},{"key":"B103","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.27715","article-title":"Association of functional IL16 polymorphisms with cancer and cardiovascular disease: a meta-analysis","volume":"11","author":"de Souza","year":"2020","journal-title":"Oncotarget"},{"key":"B104","doi-asserted-by":"publisher","DOI":"10.7314\/apjcp.2014.15.11.4697","article-title":"Positive association between IL-16 rs11556218 T\/G polymorphism and cancer risk: a meta-analysis","volume":"15","author":"Mo","year":"2014","journal-title":"Asian Pac J Cancer Prev"},{"key":"B105","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/6611085","article-title":"Anti-interleukin-16-neutralizing antibody attenuates cardiac inflammation and protects against cardiac injury in doxorubicin-treated mice","volume":"2021","author":"Zhang","year":"2021","journal-title":"Mediat Inflammation"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1524026\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,6,2]],"date-time":"2025-06-02T05:22:35Z","timestamp":1748841755000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1524026\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,2]]},"references-count":105,"alternative-id":["10.3389\/fimmu.2025.1524026"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1524026","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,2]]},"article-number":"1524026"}}