Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression
Copyright policy )Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression
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.
Receptors, CXCR5, Cancer Research, Chromatin Immunoprecipitation, Fluorescent Antibody Technique, Autoimmunity, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Real-Time Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Article, Mice, Animals, DNA Primers, Mice, Knockout, Analysis of Variance, NFATC Transcription Factors, Gene Expression Profiling, Flow Cytometry, Germinal Center, Adoptive Transfer, Immunohistochemistry, Immunity, Humoral
Receptors, CXCR5, Cancer Research, Chromatin Immunoprecipitation, Fluorescent Antibody Technique, Autoimmunity, Electrophoretic Mobility Shift Assay, Enzyme-Linked Immunosorbent Assay, Real-Time Polymerase Chain Reaction, T-Lymphocytes, Regulatory, Article, Mice, Animals, DNA Primers, Mice, Knockout, Analysis of Variance, NFATC Transcription Factors, Gene Expression Profiling, Flow Cytometry, Germinal Center, Adoptive Transfer, Immunohistochemistry, Immunity, Humoral
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