IL-21 promotes autoreactive germinal center development in BXD2 mice partially by regulating TFR. (P4116)

• DOI: 10.4049/jimmunol.190.supp.191.4
• Publication Date: 2023-01-01T22:12:38Z
• Authors: Yanna Ding; Hui-Chen Hsu; Jun Li; PingAr Yang; Allan Zajac; John Mountz
• Keywords: CXCR5

Abstract Follicular regulatory T cells (TFR) are a CD4 (Treg) subset that suppress germinal center (GC) B cell differentiation. Interleukin 21 (IL-21) promotes follicular helper (TFH) In the present study we investigated modulatory effects of IL-21 on TFR in autoimmune BXD2 mice develop spontaneous GCs with accumulation IL-21+TFH spleen. BXD2-Il21-/- mice, GL-7+Fas+GC and CXCR5+ICOS+TFHs were significantly reduced, but frequency was 2-fold higher than wild-type mice. Most CXCR5+ICOS+CD4 highly expressed Treg markers including FoxP3, CTLA4, TGF-β1 GITR. FoxP3+TFR localized spleen areas Surprisingly, transfer TFRs from into reduced IgM not IgG autoantibody producing This may be due to suppressive as administration AdIL-21 increased GC decreased ratio TFR/TFH vivo. vitro, TFH Tgfb expression by TFRs. also counteracted TFR-induced death inhibition TFHs. The suggests positively autoreactive reactions at least partially decreasing compromising function