Fig. 2From: Differentiation, functions, and roles of T follicular regulatory cells in autoimmune diseasesRepresentative signaling modulation of Tfr cell differentiation. The ICOS signaling activates the p85α-OPN-i axis and promotes Bcl-6–dependent Tfr cell differentiation. IL-2–activated STAT3 and STAT5 selectively bind to FOXP3 and BCL6 genes, respectively, thereby converting memory Tfh cells to functional Tfr cells. IL-21 inhibits Tfr cell development by blocking the pAkt signaling, thereby reducing the expression of TGF-β and Foxp3. SOSTDC1 enhances Tfr cell differentiation and function by blocking the Wnt/β-catenin axis and subsequently upregulating Foxp3, CXCR5, and CTLA-4. miR-17-92 promotes Tfr cell differentiation by enhancing the PI3K-mTORC1 signaling.Back to article page