{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T07:00:16Z","timestamp":1760598016342,"version":"3.41.2"},"reference-count":27,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T00:00:00Z","timestamp":1610323200000},"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:sec><jats:title>Objective<\/jats:title><jats:p>Gout is a chronic disease characterized by the deposition of monosodium urate (MSU) crystals in tissue. Study with a focus on adaptive immune response remains to be understood although innate immune response has been reported extensively in gout etiology. Our study attempted to investigate the association of gout-related immune cell imbalance with clinical features and comorbidity with renal impairment and the implicated pathogenesis <jats:italic>via<\/jats:italic> the assessment of T and B cell subsets in different activity phases or with immune effects combined with the analyses of clinical parameters.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Fifty-eight gout patients and 56 age- and sex-matched healthy individuals were enrolled. To learn the roles of circulating T cells, a lymphocyte profile incorporating 32 T cell subsets was tested from isolated freshly peripheral blood monocyte cells (PBMCs) with multiple-color flow cytometry. Furthermore, the collected clinical features of participants were used to analyze the characteristics of these differential cell subsets. Stratified on the basis of the level of creatinine (Cr, enzymatic method), all patients were categorized into Cr<jats:sup>low<\/jats:sup> (Cr \u2264 116 \u03bcmol\/L) and Cr<jats:sup>hi<\/jats:sup> (Cr &amp;gt; 116 \u03bcmol\/L) groups to exploit whether these gout-associated T cell subsets were functional in gout-targeted kidney dysfunction. The differentiation of B cells was investigated in gout patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results show that CD 4<jats:sup>+<\/jats:sup> T cells, Th2 cells, and Tc2 cells were upregulated, whereas Tc17 cells were downregulated. Tfh cells skewed toward the polarization of Tfh2 cells. Specifically, Tfh2 cells increased, but Tfh1 cells decreased, accompanied with aging for gout patients, suggesting that age might trigger the skewing of Tfh1\/Tfh2 cell subsets to influence gout development. Moreover, Tfh2 cells were connected to renal dysfunction as well. No alterations of B cell subsets were observed in patients when compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data demonstrate age-specific dysfunctions of Tfh1\/2 cells in gout occurrence, and Tfh2 cell upregulation is associated with gout-targeted renal dysfunction. However, Tfh2 cells may function in auto-inflammatory gout independent of helping B differentiation, and an in-depth study remains to be conducted.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2020.625458","type":"journal-article","created":{"date-parts":[[2021,1,11]],"date-time":"2021-01-11T19:24:38Z","timestamp":1610393078000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Age-Specific Imbalance of Circulating Tfh Cell Subsets and Its Association With Gout-Targeted Kidney Impairment"],"prefix":"10.3389","volume":"11","author":[{"given":"Yefei","family":"Huang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian","family":"Gui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liudan","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomin","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boxiong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yina","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuqi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiujing","family":"Wei","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiuxia","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiayong","family":"Ou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zena","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiming","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zetao","family":"Liao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linkai","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minli","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangyan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jieruo","family":"Gu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2021,1,11]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00346-9","article-title":"Gout","volume":"388","author":"Dalbeth","year":"2016","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60883-7","article-title":"Gout","volume":"375","author":"Richette","year":"2010","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1002\/art.24185","article-title":"Resident macrophages initiating and driving inflammation in a monosodium urate monohydrate crystal-induced murine peritoneal model of acute gout","volume":"60","author":"Martin","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/nature04516","article-title":"Gout-associated uric acid crystals activate the NALP3 inflammasome","volume":"440","author":"Martinon","year":"2006","journal-title":"Nature"},{"key":"B5","doi-asserted-by":"publisher","first-page":"R164","DOI":"10.1186\/ar3483","article-title":"Bone destruction by receptor activator of nuclear factor B ligand-expressing T cells in chronic gouty arthritis","volume":"13","author":"Lee","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101408","article-title":"Uric acid-driven Th17 differentiation requires inflammasome-derived IL-1 and IL-18","volume":"187","author":"Conforti-Andreoni","year":"2011","journal-title":"J Immunol"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2004.024091","article-title":"Gout epidemiology: results from the UK General Practice Research Database, 1990-1999","volume":"64","author":"Mikuls","year":"2005","journal-title":"Ann Rheum Dis"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2013.00271","article-title":"Human T Cell Aging and the Impact of Persistent Viral Infections","volume":"4","author":"F\u00fcl\u00f6p","year":"2013","journal-title":"Front Immunol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2009.05.009","article-title":"Effects of aging on T cell function","volume":"21","author":"Haynes","year":"2009","journal-title":"Curr Opin Immunol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.174.8.5016","article-title":"TLR2 signaling in chondrocytes drives calcium pyrophosphate dihydrate and monosodium urate crystal-induced nitric oxide generation","volume":"174","author":"Liu-Bryan","year":"2005","journal-title":"J Immunol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/art.21238","article-title":"Innate immunity conferred by toll-like receptors 2 and 4 and myeloid differentiation factor 88 expression is pivotal to monosodium urate monohydrate crystal-induced inflammation","volume":"52","author":"Liu-Bryan","year":"2005","journal-title":"Arthritis Rheum"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2010.12.012","article-title":"Human Blood CXCR5+CD4+ T Cells Are Counterparts of T Follicular Cells and Contain Specific Subsets that Differentially Support Antibody Secretion","volume":"34","author":"Morita","year":"2011","journal-title":"Immunity"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.clim.2015.02.016","article-title":"Alteration of circulating type 2 follicular helper T cells and regulatory B cells underlies the comorbid association of allergic rhinitis with bronchial asthma","volume":"158","author":"Kamekura","year":"2015","journal-title":"Clin Immunol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.10.012","article-title":"The Transcription Factor Ets1 Suppresses T Follicular Helper Type 2 Cell Differentiation to Halt the Onset of Systemic Lupus Erythematosus","volume":"49","author":"Kim","year":"2018","journal-title":"Immunity"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/BF00320399","article-title":"Age-related decline of human interferon alpha and interferon gamma production","volume":"48","author":"Abb","year":"1984","journal-title":"Blut: Z f\u00fcr die Gesamte Blutforschung"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01145-6","article-title":"lmmunosenescence","volume":"18","author":"Pawelec","year":"1997","journal-title":"Immunol Today"},{"key":"B17","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1007\/978-0-387-76842-7_5","article-title":"A Matter of Life and Death of T-Lymphocytes in Immunosenescence","volume-title":"Immunosenescence","author":"Gupta","year":"2007"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/nature01991","article-title":"Molecular identification of a danger signal that alerts the immune system to dying cells","volume":"425","author":"Shi","year":"2003","journal-title":"Nature"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40124","article-title":"Uric acid promotes an acute inflammatory response to sterile cell death in mice","volume":"120","author":"Kono","year":"2010","journal-title":"J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1038\/15200","article-title":"Natural adjuvants: endogenous activators of dendritic cells","volume":"5","author":"Gallucci","year":"1999","journal-title":"Nat Med"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.260497597","article-title":"Cell Injury Releases Endogenous Adjuvants that Stimulate Cytotoxic T Cell Responses","volume":"97","author":"Shi","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2011.03.015","article-title":"An unexpected role for uric acid as an inducer of T helper 2 cell immunity to inhaled antigens and inflammatory mediator of allergic asthma","volume":"34","author":"Kool","year":"2011","journal-title":"Immunity"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0b013e32834f049f","article-title":"Hyperuricemia, gout and the kidney","volume":"24","author":"Gibson","year":"2012","journal-title":"Curr Opin Rheumatol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1136\/ard.39.5.417","article-title":"Renal impairment and gout","volume":"39","author":"Gibson","year":"1980","journal-title":"Ann Rheum Dis"},{"key":"B25","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/35040504","article-title":"Interleukin 21 and its receptor are involved in NK cell expansion and regulation of lymphocyte function","volume":"408","author":"Johnston","year":"2000","journal-title":"Nature"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.9.5154","article-title":"Cutting edge: IL-21 is a switch factor for the production of IgG1 and IgG3 by human B cells","volume":"172","author":"Pene","year":"2004","journal-title":"J Immunol"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2018.09.001","article-title":"T follicular helper cells restricted by IRF8 contribute to T cell-mediated inflammation","volume":"96","author":"Zhang","year":"2019","journal-title":"J Autoimmun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.625458\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:18:33Z","timestamp":1610583513000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2020.625458\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,1,11]]},"references-count":27,"alternative-id":["10.3389\/fimmu.2020.625458"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2020.625458","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2021,1,11]]},"article-number":"625458"}}