ICOS/ICOSL signaling is important in maintaining Tfh polarization.216 Downregulation of CXCR5 and upregulation of CCR7 induced by ICOS inhibition could result in the reversal of Tfh polarization and exit from B-cell follicles.214 Due to the importance of humoral immunity in adaptive immunity, there is no doubt that Tfh cells play an important role in immune function and autoimmune diseases (Figure 3). Here, ICOS is linked to autoimmune disease.