title: Follicular regulatory T cells control humoral autoimmunity via NFAT2-regulated CXCR5 expression.
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.
authors.affiliation: Department of Molecular Pathology, Institute of Pathology and 4 Comprehensive Cancer Center Mainfranken, Julius-Maximilians-University of Wuerzburg, 97080 Wuerzburg, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Vaeth
authors.forename: Gerd
authors.initials: G
authors.lastname: Müller
authors.forename: Dennis
authors.initials: D
authors.lastname: Stauss
authors.forename: Lena
authors.initials: L
authors.lastname: Dietz
authors.forename: Stefan
authors.initials: S
authors.lastname: Klein-Hessling
authors.forename: Edgar
authors.initials: E
authors.lastname: Serfling
authors.forename: Martin
authors.initials: M
authors.lastname: Lipp
authors.forename: Ingolf
authors.initials: I
authors.lastname: Berberich
authors.forename: Friederike
authors.initials: F
authors.lastname: Berberich-Siebelt
mesh_terms: D019264:Adoptive Transfer; D000704:Analysis of Variance; D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D024202:Electrophoretic Mobility Shift Assay; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D020869:Gene Expression Profiling; D018858:Germinal Center / Q000276:immunology*; D056724:Immunity, Humoral / Q000276:immunology*; D007150:Immunohistochemistry; D051379:Mice; D018345:Mice, Knockout; D050778:NFATC Transcription Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D054380:Receptors, CXCR5 / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C513179:CXCR5 protein, mouse; D017931:DNA Primers; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; D054380:Receptors, CXCR5