{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T17:19:30Z","timestamp":1793812770574,"version":"4.6.1"},"reference-count":93,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["#179765"],"award-info":[{"award-number":["#179765"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["191718"],"award-info":[{"award-number":["191718"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CIHR REDI Early Career Transition Award"},{"name":"CIHR doctoral award"},{"DOI":"10.13039\/501100019691","name":"University of Alberta Faculty of Medicine and Dentistry Advanced Cell Exploration Core","doi-asserted-by":"publisher","award":["RRID:SCR_019182"],"award-info":[{"award-number":["RRID:SCR_019182"]}],"id":[{"id":"10.13039\/501100019691","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Faculty of Medicine and Dentistry"},{"name":"Li Ka Shing Institute of Virology"},{"name":"Striving for Pandemic Preparedness\u2014The Alberta Research Consortium"},{"DOI":"10.13039\/501100001805","name":"Canada Foundation for Innovation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001805","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Interleukin-17 (IL-17) plays a central role in the pathogenesis of various autoimmune diseases. Soluble CD14 (sCD14), a marker of innate immune activation, is elevated in several inflammatory conditions. However, its influence on IL-17 production and the differentiation of Th17 cells remains poorly understood. We found that sCD14 enhances Th17-associated cytokine production and up-regulates critical transcription factors such as STAT3 and RORC. Notably, sCD14's effect on Th17 polarization was mediated indirectly through autologous sCD14-treated peripheral blood mononuclear cell (PBMC) supernatant (sCD14-PBMC-Sup). Additionally, we identified a distinct cytokine profile enriched for pro-inflammatory cytokines and chemokines in sCD14-treated T cells, further reinforcing the Th17-promoting role of sCD14. Interestingly, gamma-aminobutyric acid (GABA), a metabolite elevated in sCD14-treated monocytes, was identified as a potential contributor to Th17 polarization. GABA supplementation in T-cell cultures enhanced IL-17A secretion, indicating its role as a signaling molecule in T-cell differentiation. Our findings also revealed the expansion of innate lymphoid cell (ILC)2\/3-like cells in T-cell cultures exposed to sCD14-PBMC-Sup and GABA, highlighting the potential role of monocytes in Th17-mediated immunity. Furthermore, while sCD14 promoted Th17 polarization, it simultaneously impaired T-cell activation and proliferation, suggesting an immunosuppressive effect mediated by soluble factors released from monocytes. These results underscore the dual role of sCD14 in modulating T-cell responses, promoting Th17 differentiation while suppressing T-cell effector functions. This study identifies a previously unrecognized role for sCD14 in promoting Th17 induction, highlighting its contribution to immune regulation and its potential as a therapeutic target in Th17-driven autoimmune conditions.<\/jats:p>\n                  <jats:p>Classification: Immunology<\/jats:p>","DOI":"10.1093\/pnasnexus\/pgaf406","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T03:11:53Z","timestamp":1766977913000},"source":"Crossref","is-referenced-by-count":3,"title":["Soluble CD14 promotes Th17 expansion and differentiation through gamma-aminobutyric acid and expands non-canonical innate lymphoid cells"],"prefix":"10.1093","volume":"5","author":[{"given":"Shima","family":"Shahbaz","sequence":"first","affiliation":[{"name":"Division of Foundational Sciences, Mike Petryk School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2E1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-5199-2337","authenticated-orcid":false,"given":"Amirhossein","family":"Rahmati","sequence":"additional","affiliation":[{"name":"Division of Foundational Sciences, Mike Petryk School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2E1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hussain","family":"Syed","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology, Department of Medicine, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2E1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7215-2009","authenticated-orcid":false,"given":"Shokrollah","family":"Elahi","sequence":"additional","affiliation":[{"name":"Division of Foundational Sciences, Mike Petryk School of Dentistry, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2E1","place":["Canada"]},{"name":"Li Ka Shing Institute of Virology, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2R3","place":["Canada"]},{"name":"Women and Children Health Research Institute, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 1C9","place":["Canada"]},{"name":"Cancer Research Institute of Northern Alberta, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2E1","place":["Canada"]},{"name":"Glycomics Institute of Alberta, University of Alberta , Edmonton, AB , T6G 2G2","place":["Canada"]},{"name":"Alberta Transplant Institute, Faculty of Medicine and Dentistry, University of Alberta , Edmonton, AB , T6G 2E1","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"2026051215032540600_pgaf406-B1","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1038\/nature18848","article-title":"The microbiota in adaptive immune homeostasis and disease","volume":"535","author":"Honda","year":"2016","journal-title":"Nature"},{"key":"2026051215032540600_pgaf406-B2","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.immuni.2019.03.021","article-title":"The IL-17 family of cytokines in health and disease","volume":"50","author":"McGeachy","year":"2019","journal-title":"Immunity"},{"key":"2026051215032540600_pgaf406-B3","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1093\/rheumatology\/kex301","article-title":"Secukinumab sustains improvement in signs and symptoms of psoriatic arthritis: 2 year results from the phase 3 FUTURE 2 study","volume":"56","author":"McInnes","year":"2017","journal-title":"Rheumatology (Oxford)"},{"key":"2026051215032540600_pgaf406-B4","doi-asserted-by":"crossref","first-page":"15505","DOI":"10.1073\/pnas.0710686105","article-title":"Generation and regulation of human CD4+ IL-17-producing T cells in ovarian cancer","volume":"105","author":"Miyahara","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026051215032540600_pgaf406-B5","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/j.cell.2006.07.035","article-title":"The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells","volume":"126","author":"Ivanov","year":"2006","journal-title":"Cell"},{"key":"2026051215032540600_pgaf406-B6","doi-asserted-by":"crossref","first-page":"e2006649","DOI":"10.1371\/journal.pbio.2006649","article-title":"CD71 + VISTA+ erythroid cells promote the development and function of regulatory T cells through TGF-beta","volume":"16","author":"Shahbaz","year":"2018","journal-title":"PLoS Biol"},{"key":"2026051215032540600_pgaf406-B7","doi-asserted-by":"crossref","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and Th17 cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"2026051215032540600_pgaf406-B8","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1038\/nature05970","article-title":"IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells","volume":"448","author":"Korn","year":"2007","journal-title":"Nature"},{"key":"2026051215032540600_pgaf406-B9","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.immuni.2009.02.007","article-title":"Critical regulation of early Th17 cell differentiation by interleukin-1 signaling","volume":"30","author":"Chung","year":"2009","journal-title":"Immunity"},{"key":"2026051215032540600_pgaf406-B10","doi-asserted-by":"crossref","first-page":"5948","DOI":"10.4049\/jimmunol.181.9.5948","article-title":"IL-23 promotes maintenance but not commitment to the Th17 lineage","volume":"181","author":"Stritesky","year":"2008","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B11","doi-asserted-by":"crossref","first-page":"2036","DOI":"10.1016\/j.cell.2020.12.008","article-title":"Serum amyloid a proteins induce pathogenic Th17 cells and promote inflammatory disease","volume":"183","author":"Lee","year":"2020","journal-title":"Cell"},{"key":"2026051215032540600_pgaf406-B12","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1084\/jem.20082293","article-title":"Prostaglandin E2 regulates Th17 cell differentiation and function through cyclic AMP and EP2\/EP4 receptor signaling","volume":"206","author":"Boniface","year":"2009","journal-title":"J Exp Med"},{"key":"2026051215032540600_pgaf406-B13","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1084\/jem.20110278","article-title":"HIF1alpha-dependent glycolytic pathway orchestrates a metabolic checkpoint for the differentiation of TH17 and Treg cells","volume":"208","author":"Shi","year":"2011","journal-title":"J Exp Med"},{"key":"2026051215032540600_pgaf406-B14","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1038\/nm0415-414d","article-title":"De novo fatty acid synthesis controls the fate between regulatory T and T helper 17 cells","volume":"21","author":"Berod","year":"2015","journal-title":"Nat Med"},{"key":"2026051215032540600_pgaf406-B15","doi-asserted-by":"crossref","first-page":"1780","DOI":"10.1016\/j.cell.2018.10.001","article-title":"Distinct regulation of Th17 and Th1 cell differentiation by glutaminase-dependent metabolism","volume":"175","author":"Johnson","year":"2018","journal-title":"Cell"},{"key":"2026051215032540600_pgaf406-B16","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/0896-6273(91)90077-D","article-title":"Two genes encode distinct glutamate decarboxylases","volume":"7","author":"Erlander","year":"1991","journal-title":"Neuron"},{"key":"2026051215032540600_pgaf406-B17","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1002\/JLB.3HI0720-431R","article-title":"GABAergic signaling in human and murine NK cells upon challenge with toxoplasma gondii","volume":"110","author":"Bhandage","year":"2021","journal-title":"J Leukoc Biol"},{"key":"2026051215032540600_pgaf406-B18","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1038\/s41586-021-04082-1","article-title":"B cell-derived GABA elicits IL-10(+) macrophages to limit anti-tumour immunity","volume":"599","author":"Zhang","year":"2021","journal-title":"Nature"},{"key":"2026051215032540600_pgaf406-B19","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.ebiom.2018.03.019","article-title":"GABA regulates release of inflammatory cytokines from peripheral blood mononuclear cells and CD4+ T cells and is immunosuppressive in type 1 diabetes","volume":"30","author":"Bhandage","year":"2018","journal-title":"Ebiomedicine"},{"key":"2026051215032540600_pgaf406-B20","first-page":"685","article-title":"Intestinal microbiota-derived GABA mediates interleukin-17 expression during enterotoxigenic Escherichia coli infection","volume":"7","author":"Ren","year":"2016","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B21","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3389\/fimmu.2018.00795","article-title":"A reappraisal on the potential ability of human neutrophils to express and produce IL-17 family members in vitro: failure to reproducibly detect it","volume":"9","author":"Tamassia","year":"2018","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B22","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1038\/s41577-020-0282-9","article-title":"Plasticity of innate lymphoid cell subsets","volume":"20","author":"Bal","year":"2020","journal-title":"Nat Rev Immunol"},{"key":"2026051215032540600_pgaf406-B23","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1038\/ni.3482","article-title":"NK cells and type 1 innate lymphoid cells: partners in host defense","volume":"17","author":"Spits","year":"2016","journal-title":"Nat Immunol"},{"key":"2026051215032540600_pgaf406-B24","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/ni.1668","article-title":"Human fetal lymphoid tissue-inducer cells are interleukin 17-producing precursors to RORC+ CD127+ natural killer-like cells","volume":"10","author":"Cupedo","year":"2009","journal-title":"Nat Immunol"},{"key":"2026051215032540600_pgaf406-B25","doi-asserted-by":"crossref","first-page":"634","DOI":"10.1016\/j.immuni.2012.06.020","article-title":"The transcription factor GATA-3 controls cell fate and maintenance of type 2 innate lymphoid cells","volume":"37","author":"Hoyler","year":"2012","journal-title":"Immunity"},{"key":"2026051215032540600_pgaf406-B26","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1038\/ni.3444","article-title":"IL-1beta, IL-4 and IL-12 control the fate of group 2 innate lymphoid cells in human airway inflammation in the lungs","volume":"17","author":"Bal","year":"2016","journal-title":"Nat Immunol"},{"key":"2026051215032540600_pgaf406-B27","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1038\/nature11813","article-title":"A T-bet gradient controls the fate and function of CCR6-RORgammat+ innate lymphoid cells","volume":"494","author":"Klose","year":"2013","journal-title":"Nature"},{"key":"2026051215032540600_pgaf406-B28","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1084\/jem.20151750","article-title":"IL-12 drives functional plasticity of human group 2 innate lymphoid cells","volume":"213","author":"Lim","year":"2016","journal-title":"J Exp Med"},{"key":"2026051215032540600_pgaf406-B29","doi-asserted-by":"crossref","first-page":"547","DOI":"10.4049\/jimmunol.141.2.547","article-title":"The monocyte differentiation antigen, CD14, is anchored to the cell membrane by a phosphatidylinositol linkage","volume":"141","author":"Haziot","year":"1988","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B30","doi-asserted-by":"crossref","first-page":"3909","DOI":"10.4049\/jimmunol.137.12.3909","article-title":"Biochemistry and expression of myelomonocytic antigens","volume":"137","author":"Goyert","year":"1986","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B31","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1016\/j.cell.2011.09.051","article-title":"CD14 controls the LPS-induced endocytosis of Toll-like receptor 4","volume":"147","author":"Zanoni","year":"2011","journal-title":"Cell"},{"key":"2026051215032540600_pgaf406-B32","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nri2079","article-title":"The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling","volume":"7","author":"O'Neill","year":"2007","journal-title":"Nat Rev Immunol"},{"key":"2026051215032540600_pgaf406-B33","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1111\/imm.13634","article-title":"Role of CD14 in human disease","volume":"169","author":"Sharygin","year":"2023","journal-title":"Immunology"},{"key":"2026051215032540600_pgaf406-B34","doi-asserted-by":"crossref","first-page":"2179","DOI":"10.2337\/db10-1210","article-title":"CD14 modulates inflammation-driven insulin resistance","volume":"60","author":"Fernandez-Real","year":"2011","journal-title":"Diabetes"},{"key":"2026051215032540600_pgaf406-B35","doi-asserted-by":"crossref","first-page":"1233","DOI":"10.1007\/s00018-020-03656-y","article-title":"TLR4 and CD14 trafficking and its influence on LPS-induced pro-inflammatory signaling","volume":"78","author":"Ciesielska","year":"2021","journal-title":"Cell Mol Life Sci"},{"key":"2026051215032540600_pgaf406-B36","doi-asserted-by":"crossref","first-page":"11471","DOI":"10.3390\/ijms241411471","article-title":"Immune system and hepatocellular carcinoma (HCC): new insights into HCC progression","volume":"24","author":"Kotsari","year":"2023","journal-title":"Int J Mol Sci"},{"key":"2026051215032540600_pgaf406-B37","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1128\/IAI.69.6.3772-3781.2001","article-title":"CD14 is expressed and released as soluble CD14 by human intestinal epithelial cells in vitro: lipopolysaccharide activation of epithelial cells revisited","volume":"69","author":"Funda","year":"2001","journal-title":"Infect Immun"},{"key":"2026051215032540600_pgaf406-B38","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1097\/QAD.0000000000000735","article-title":"Soluble CD14 is a nonspecific marker of monocyte activation","volume":"29","author":"Shive","year":"2015","journal-title":"AIDS"},{"key":"2026051215032540600_pgaf406-B39","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1097\/QAI.0b013e3182237e54","article-title":"Plasma sCD14 is a biomarker associated with impaired neurocognitive test performance in attention and learning domains in HIV infection","volume":"57","author":"Lyons","year":"2011","journal-title":"J Acquir Immune Defic Syndr"},{"key":"2026051215032540600_pgaf406-B40","doi-asserted-by":"crossref","first-page":"1341843","DOI":"10.3389\/fimmu.2024.1341843","article-title":"Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome","volume":"15","author":"Saito","year":"2024","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B41","doi-asserted-by":"crossref","first-page":"e0125623","DOI":"10.1128\/spectrum.01256-23","article-title":"Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and omicron variant, identifies differential immune profiles","volume":"11","author":"Shahbaz","year":"2023","journal-title":"Microbiol Spectr"},{"key":"2026051215032540600_pgaf406-B42","doi-asserted-by":"crossref","first-page":"4470","DOI":"10.4049\/jimmunol.172.7.4470","article-title":"CD14 is an acute-phase protein","volume":"172","author":"Bas","year":"2004","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B43","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1053\/j.gastro.2011.06.063","article-title":"Host response to translocated microbial products predicts outcomes of patients with HBV or HCV infection","volume":"141","author":"Sandler","year":"2011","journal-title":"Gastroenterology"},{"key":"2026051215032540600_pgaf406-B44","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1002\/(SICI)1521-4141(199901)29:01<265::AID-IMMU265>3.0.CO;2-G","article-title":"Soluble CD14 acts as a negative regulator of human T cell activation and function","volume":"29","author":"Nores","year":"1999","journal-title":"Eur J Immunol"},{"key":"2026051215032540600_pgaf406-B45","doi-asserted-by":"crossref","first-page":"907","DOI":"10.1038\/icb.2016.66","article-title":"New roles for CD14 and IL-beta linking inflammatory dendritic cells to IL-17 production in memory CD4(+) T cells","volume":"94","author":"Ilarregui","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"2026051215032540600_pgaf406-B46","doi-asserted-by":"crossref","first-page":"103267","DOI":"10.1016\/j.jaut.2024.103267","article-title":"Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome","volume":"147","author":"Saito","year":"2024","journal-title":"J Autoimmun"},{"key":"2026051215032540600_pgaf406-B47","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bbi.2024.11.032","article-title":"Upregulation of olfactory receptors and neuronal-associated genes highlights complex immune and neuronal dysregulation in Long COVID patients","volume":"124","author":"Shahbaz","year":"2025","journal-title":"Brain Behav Immun"},{"key":"2026051215032540600_pgaf406-B48","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/j.stemcr.2021.04.001","article-title":"Erythroid precursors and progenitors suppress adaptive immunity and get invaded by SARS-CoV-2","volume":"16","author":"Shahbaz","year":"2021","journal-title":"Stem Cell Reports"},{"key":"2026051215032540600_pgaf406-B49","doi-asserted-by":"crossref","first-page":"2474","DOI":"10.4049\/jimmunol.1901481","article-title":"Galectin-9 and VISTA expression define terminally exhausted T cells in HIV-1 infection","volume":"204","author":"Shahbaz","year":"2020","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B50","doi-asserted-by":"crossref","first-page":"1202","DOI":"10.1093\/jimmun\/vkaf020","article-title":"Galectin-3 regulates erythropoiesis and enhances the immunoregulatory properties of CD71+ erythroid cells across developmental stages","volume":"214","author":"Elahi","year":"2025","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B51","doi-asserted-by":"crossref","first-page":"e1289","DOI":"10.1002\/cti2.1289","article-title":"Differential transcriptional and functional properties of regulatory T cells in HIV-infected individuals on antiretroviral therapy and long-term non-progressors","volume":"10","author":"Shahbaz","year":"2021","journal-title":"Clin Transl Immunol"},{"key":"2026051215032540600_pgaf406-B52","doi-asserted-by":"crossref","first-page":"e1010378","DOI":"10.1371\/journal.ppat.1010378","article-title":"Elevated ATP via enhanced miRNA-30b, 30c, and 30e downregulates the expression of CD73 in CD8+ T cells of HIV-infected individuals","volume":"18","author":"Shahbaz","year":"2022","journal-title":"PLoS Pathog"},{"key":"2026051215032540600_pgaf406-B53","doi-asserted-by":"crossref","first-page":"e0159924","DOI":"10.1128\/mbio.01599-24","article-title":"Bipotential B-neutrophil progenitors are present in human and mouse bone marrow and emerge in the periphery upon stress hematopoiesis","volume":"15","author":"Shahbaz","year":"2024","journal-title":"mBio"},{"key":"2026051215032540600_pgaf406-B54","doi-asserted-by":"crossref","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2026051215032540600_pgaf406-B55","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s13059-019-1874-1","article-title":"Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression","volume":"20","author":"Hafemeister","year":"2019","journal-title":"Genome Biol"},{"key":"2026051215032540600_pgaf406-B56","doi-asserted-by":"crossref","first-page":"giy083","DOI":"10.1093\/gigascience\/giy083","article-title":"Clustering trees: a visualization for evaluating clusterings at multiple resolutions","volume":"7","author":"Zappia","year":"2018","journal-title":"Gigascience"},{"key":"2026051215032540600_pgaf406-B57","doi-asserted-by":"crossref","first-page":"2485","DOI":"10.1093\/bioinformatics\/btab003","article-title":"Nebulosa recovers single-cell gene expression signals by kernel density estimation","volume":"37","author":"Alquicira-Hernandez","year":"2021","journal-title":"Bioinformatics"},{"key":"2026051215032540600_pgaf406-B58","doi-asserted-by":"crossref","first-page":"1021928","DOI":"10.3389\/fimmu.2022.1021928","article-title":"Differential effects of age, sex and dexamethasone therapy on ACE2\/TMPRSS2 expression and susceptibility to SARS-CoV-2 infection","volume":"13","author":"Shahbaz","year":"2022","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B59","doi-asserted-by":"crossref","first-page":"e00384-21","DOI":"10.1128\/mBio.00384-21","article-title":"Galectin-9, a player in cytokine release syndrome and a surrogate diagnostic biomarker in SARS-CoV-2 infection","volume":"12","author":"Bozorgmehr","year":"2021","journal-title":"mBio"},{"key":"2026051215032540600_pgaf406-B60","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1038\/nm.2422","article-title":"Protective HIV-specific CD8+ T cells evade Treg cell suppression","volume":"17","author":"Elahi","year":"2011","journal-title":"Nat Med"},{"key":"2026051215032540600_pgaf406-B61","doi-asserted-by":"crossref","first-page":"7728","DOI":"10.1038\/s41598-017-07938-7","article-title":"CD71+ erythroid suppressor cells impair adaptive immunity against Bordetella pertussis","volume":"7","author":"Namdar","year":"2017","journal-title":"Sci Rep"},{"key":"2026051215032540600_pgaf406-B62","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1093\/ecco-jcc\/jjy186","article-title":"The profile of human milk metabolome, cytokines, and antibodies in inflammatory bowel diseases versus healthy mothers, and potential impact on the newborn","volume":"13","author":"Meng","year":"2019","journal-title":"J Crohns Colitis"},{"key":"2026051215032540600_pgaf406-B63","doi-asserted-by":"crossref","first-page":"5868","DOI":"10.4049\/jimmunol.152.12.5868","article-title":"Recombinant soluble CD14 inhibits LPS-induced tumor necrosis factor-alpha production by cells in whole blood","volume":"152","author":"Haziot","year":"1994","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B64","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1111\/j.1365-3083.1995.tb03634.x","article-title":"Influence of CD14, LBP and BPI in the monocyte response to LPS of different polysaccharide chain length","volume":"42","author":"Jahr","year":"1995","journal-title":"Scand J Immunol"},{"key":"2026051215032540600_pgaf406-B65","doi-asserted-by":"crossref","first-page":"3036","DOI":"10.3389\/fimmu.2018.03036","article-title":"Metabolic checkpoints in differentiation of helper T cells in tissue inflammation","volume":"9","author":"Roy","year":"2018","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B66","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1084\/jem.20122494","article-title":"T cell-derived inducible nitric oxide synthase switches off Th17 cell differentiation","volume":"210","author":"Jianjun","year":"2013","journal-title":"J Exp Med"},{"key":"2026051215032540600_pgaf406-B67","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1038\/ni.2416","article-title":"Induction and molecular signature of pathogenic TH17 cells","volume":"13","author":"Lee","year":"2012","journal-title":"Nat Immunol"},{"key":"2026051215032540600_pgaf406-B68","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/s41590-025-02081-2","article-title":"Enteric GABAergic neuron-derived gamma-aminobutyric acid initiates expression of Igfbp7 to sustain ILC3 homeostasis","volume":"26","author":"Liu","year":"2025","journal-title":"Nat Immunol"},{"key":"2026051215032540600_pgaf406-B69","doi-asserted-by":"crossref","first-page":"1689","DOI":"10.3390\/cells9071689","article-title":"Soluble CD14 induces pro-inflammatory cytokines in rheumatoid arthritis fibroblast-like synovial cells via toll-like receptor 4","volume":"9","author":"Ichise","year":"2020","journal-title":"Cells"},{"key":"2026051215032540600_pgaf406-B70","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1161\/ATVBAHA.112.300421","article-title":"Soluble CD14: genomewide association analysis and relationship to cardiovascular risk and mortality in older adults","volume":"33","author":"Reiner","year":"2013","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2026051215032540600_pgaf406-B71","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1111\/j.1365-2249.1994.tb06222.x","article-title":"Elevated levels of soluble CD14 in serum of patients with systemic lupus erythematosus","volume":"96","author":"Nockher","year":"1994","journal-title":"Clin Exp Immunol"},{"key":"2026051215032540600_pgaf406-B72","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1093\/infdis\/jis545","article-title":"Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection","volume":"206","author":"Kelesidis","year":"2012","journal-title":"J Infect Dis"},{"key":"2026051215032540600_pgaf406-B73","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.immuni.2013.10.001","article-title":"Systemic effects of inflammation on health during chronic HIV infection","volume":"39","author":"Deeks","year":"2013","journal-title":"Immunity"},{"key":"2026051215032540600_pgaf406-B74","doi-asserted-by":"crossref","first-page":"1099","DOI":"10.4049\/jimmunol.2100446","article-title":"The quality of SARS-CoV-2\u2013specific T cell functions differs in patients with mild\/moderate versus severe disease, and T cells expressing coinhibitory receptors are highly activated","volume":"207","author":"Shahbaz","year":"2021","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B75","doi-asserted-by":"crossref","first-page":"1443363","DOI":"10.3389\/fimmu.2024.1443363","article-title":"Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function","volume":"15","author":"Elahi","year":"2024","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B76","doi-asserted-by":"crossref","first-page":"102449","DOI":"10.1016\/j.xcrm.2025.102449","article-title":"Integrated immune, hormonal, and transcriptomic profiling reveals sex-specific dysregulation in long COVID patients with ME\/CFS","volume":"6","author":"Shahbaz","year":"2025","journal-title":"Cell Rep Med"},{"key":"2026051215032540600_pgaf406-B77","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1023\/A:1021948214742","article-title":"Production of TARC and MDC by naive T cells in asthmatic patients","volume":"23","author":"Hirata","year":"2003","journal-title":"J Clin Immunol"},{"key":"2026051215032540600_pgaf406-B78","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1189\/jlb.68.3.400","article-title":"Macrophage-derived chemokine (MDC)","volume":"68","author":"Mantovani","year":"2000","journal-title":"J Leukoc Biol"},{"key":"2026051215032540600_pgaf406-B79","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1016\/j.cellimm.2005.08.032","article-title":"The expression of CCL2 by T lymphocytes of mammary tumor bearers: role of tumor-derived factors","volume":"235","author":"Owen","year":"2005","journal-title":"Cell Immunol"},{"key":"2026051215032540600_pgaf406-B80","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.4049\/jimmunol.1202222","article-title":"CD8+ T cells produce the chemokine CXCL10 in response to CD27\/CD70 costimulation to promote generation of the CD8+ effector T cell pool","volume":"191","author":"Peperzak","year":"2013","journal-title":"J Immunol"},{"key":"2026051215032540600_pgaf406-B81","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1074\/jbc.274.2.607","article-title":"The role of Tec protein-tyrosine kinase in T cell signaling","volume":"274","author":"Yang","year":"1999","journal-title":"J Biol Chem"},{"key":"2026051215032540600_pgaf406-B82","doi-asserted-by":"crossref","first-page":"182549","DOI":"10.1155\/2014\/182549","article-title":"Generation of IL-8 and IL-9 producing CD4+ T cells is affected by Th17 polarizing conditions and AHR ligands","volume":"2014","author":"Gasch","year":"2014","journal-title":"Mediators Inflamm"},{"key":"2026051215032540600_pgaf406-B83","doi-asserted-by":"crossref","first-page":"2580","DOI":"10.1073\/pnas.0915139107","article-title":"Inhibitory role for GABA in autoimmune inflammation","volume":"107","author":"Bhat","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2026051215032540600_pgaf406-B84","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1016\/j.neuropharm.2010.11.007","article-title":"An intrinsic GABAergic system in human lymphocytes","volume":"60","author":"Dionisio","year":"2011","journal-title":"Neuropharmacology"},{"key":"2026051215032540600_pgaf406-B85","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.jneuroim.2008.08.017","article-title":"GABA, a natural immunomodulator of T lymphocytes","volume":"205","author":"Bjurstom","year":"2008","journal-title":"J Neuroimmunol"},{"key":"2026051215032540600_pgaf406-B86","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s00726-011-1193-7","article-title":"GABA is an effective immunomodulatory molecule","volume":"45","author":"Jin","year":"2013","journal-title":"Amino Acids"},{"key":"2026051215032540600_pgaf406-B87","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1016\/j.immuni.2021.07.019","article-title":"An in vitro platform supports generation of human innate lymphoid cells from CD34 hematopoietic progenitors that recapitulate ex vivo identity","volume":"54","author":"Hern\u00e1ndez","year":"2021","journal-title":"Immunity"},{"key":"2026051215032540600_pgaf406-B88","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.cell.2017.02.021","article-title":"Systemic human ILC precursors provide a substrate for tissue ILC differentiation","volume":"168","author":"Lim","year":"2017","journal-title":"Cell"},{"key":"2026051215032540600_pgaf406-B89","doi-asserted-by":"crossref","first-page":"e1008696","DOI":"10.1371\/journal.ppat.1008696","article-title":"Selective upregulation of CTLA-4 on CD8+ T cells restricted by HLA-B*35Px renders them to an exhausted phenotype in HIV-1 infection","volume":"16","author":"Elahi","year":"2020","journal-title":"PLoS Pathog"},{"key":"2026051215032540600_pgaf406-B90","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1038\/s41385-018-0111-7","article-title":"Slc6a13 deficiency promotes Th17 responses during intestinal bacterial infection","volume":"12","author":"Ren","year":"2019","journal-title":"Mucosal Immunol"},{"key":"2026051215032540600_pgaf406-B91","doi-asserted-by":"crossref","first-page":"1114350","DOI":"10.3389\/fimmu.2023.1114350","article-title":"Understanding the function of the GABAergic system and its potential role in rheumatoid arthritis","volume":"14","author":"Shan","year":"2023","journal-title":"Front Immunol"},{"key":"2026051215032540600_pgaf406-B92","doi-asserted-by":"crossref","first-page":"6259","DOI":"10.1016\/S0021-9258(18)38112-2","article-title":"N-omega-hydroxy-L-arginine is an intermediate in the biosynthesis of nitric oxide from L-arginine","volume":"266","author":"Stuehr","year":"1991","journal-title":"J Biol Chem"},{"key":"2026051215032540600_pgaf406-B93","doi-asserted-by":"crossref","first-page":"e1303585","DOI":"10.1080\/2162402X.2017.1303585","article-title":"TIE-2 expressing monocytes in human cancers","volume":"6","author":"Turrini","year":"2017","journal-title":"Oncoimmunology"}],"container-title":["PNAS Nexus"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/pnasnexus\/advance-article-pdf\/doi\/10.1093\/pnasnexus\/pgaf406\/66141786\/pgaf406.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/5\/1\/pgaf406\/66141786\/pgaf406.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article-pdf\/5\/1\/pgaf406\/66141786\/pgaf406.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T19:03:44Z","timestamp":1778612624000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/pnasnexus\/article\/doi\/10.1093\/pnasnexus\/pgaf406\/8405888"}},"subtitle":[],"editor":[{"given":"Zhiqiang","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,12,29]]},"references-count":93,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1,5]]}},"URL":"https:\/\/doi.org\/10.1093\/pnasnexus\/pgaf406","relation":{},"ISSN":["2752-6542"],"issn-type":[{"value":"2752-6542","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,1]]},"published":{"date-parts":[[2025,12,29]]},"article-number":"pgaf406"}}