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IL-21 restricts T follicular regulatory T cell proliferation through Bcl-6 mediated inhibition of responsiveness to IL-2.

Jandl, Christoph; Liu, Sue M; Cañete, Pablo F; Warren, Joanna; Hughes, William E; Vogelzang, Alexis; Webster, Kylie; Craig, Maria E; Uzel, Gulbu; Dent, Alexander; Stepensky, Polina; Keller, Bärbel; Warnatz, Klaus; Sprent, Jonathan; King, Cecile.
Nat Commun; 8: 14647, 2017 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-28303891
T follicular regulatory (Tfr) cells control the magnitude and specificity of the germinal centre reaction, but how regulation is contained to ensure generation of high-affinity antibody is unknown. Here we show that this balance is maintained by the reciprocal influence of interleukin (IL)-2 and IL-21. The number of IL-2-dependent FoxP3+ regulatory T cells is increased in the peripheral blood of human patients with loss-of-function mutations in the IL-21 receptor (IL-21R). In mice, IL-21:IL-21R interactions influence the phenotype of T follicular cells, reducing the expression of CXCR4 and inhibiting the expansion of Tfr cells after T-cell-dependent immunization. The negative effect of IL-21 on Tfr cells in mice is cell intrinsic and associated with decreased expression of the high affinity IL-2 receptor (CD25). Bcl-6, expressed in abundance in Tfr cells, inhibits CD25 expression and IL-21-mediated inhibition of CD25 is Bcl-6 dependent. These findings identify a mechanism by which IL-21 reinforces humoral immunity by restricting Tfr cell proliferation.
Selo DaSilva