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Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression

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Item Type:Article
Title:Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression
Creators Name:Vaeth, M. and Mueller, G. and Stauss, D. and Dietz, L. and Klein-Hessling, S. and Serfling, E. and Lipp, M. and Berberich, I. and Berberich-Siebelt, F.
Abstract:Maturation of high-affinity B lymphocytes is precisely controlled during the germinal center reaction. This is dependent on CD4(+)CXCR5(+) follicular helper T cells (TFH) and inhibited by CD4(+)CXCR5(+)Foxp3(+) follicular regulatory T cells (TFR). Because NFAT2 was found to be highly expressed and activated in follicular T cells, we addressed its function herein. Unexpectedly, ablation of NFAT2 in T cells caused an augmented GC reaction upon immunization. Consistently, however, TFR cells were clearly reduced in the follicular T cell population due to impaired homing to B cell follicles. This was TFR-intrinsic because only in these cells NFAT2 was essential to up-regulate CXCR5. The physiological relevance for humoral (auto-)immunity was corroborated by exacerbated lupuslike disease in the presence of NFAT2-deficient TFR cells.
Keywords:Adoptive Transfer, Analysis of Variance, Autoimmunity, Chromatin Immunoprecipitation, DNA Primers, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Fluorescent Antibody Technique, Gene Expression Profiling, Germinal Center, Humoral Immunity, Immunohistochemistry, NFATC Transcription Factors, Real-Time Polymerase Chain Reaction, CXCR5 Receptors, Regulatory T-Lymphocytes, Animals, Mice
Source:Journal of Experimental Medicine
ISSN:0022-1007
Publisher:Rockefeller University Press (U.S.A.)
Volume:211
Number:3
Page Range:545-561
Date:10 March 2014
Official Publication:https://doi.org/10.1084/jem.20130604
PubMed:View item in PubMed

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