STAT3 and viral infectious disease: While IL-21 alone is not required in regulating Tfh differentiation, in combination with IL-6, IL-21 promotes Tfh differentiation by activating the STAT3 signaling cascade in vitro.20,119 IL-21 is a part of the IL-2 family of cytokines, including IL-2, IL-4, IL-7, IL-9, and IL-15, that share the common γ-chain (γc) IL-2R subunit.120 Both IL-6 and IL-12 can induce IL-21 expression in murine CD4+ T cells in vitro and in vivo.4,121,122 However, mice deficient in IL-21R have no defect in Bcl6 expression or in Tfh differentiation during viral infections.80,114,123