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

M Vaeth, G Müller, D Stauss, L Dietz… - Journal of Experimental …, 2014 - rupress.org
M Vaeth, G Müller, D Stauss, L Dietz, S Klein-Hessling, E Serfling, M Lipp, I Berberich…
Journal of Experimental Medicine, 2014rupress.org
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 …
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.
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