The costimulatory molecule ICOS regulates the expression of c-Maf and IL-21 in the development of follicular T helper cells and TH-17 cells

The inducible costimulatory molecule ICOS has been suggested to be important in the development of interleukin 17 (IL-17)producing helper T cells (T-H-17 cells) and of follicular helper T cells (T-FH cells). Here we show that ICOS-deficient mice had no defect in T-H-17 differentiation but had fewer T-H-17 cells after IL-23 stimulation and fewer TFH cells. We also show that TFH cells produced IL-17 and that TFH cells in ICOS-deficient mice were defective in IL-17 production. Both T-H-17 and TFH cells had higher expression of the transcription factor c-Maf. Genetic loss of c-Maf resulted in a defect in IL-21 production and fewer T-H-17 and T-FH cells. Thus our data suggest that ICOS-induced c-Maf regulates IL-21 production that in turn regulates the expansion of T-H-17 and T-FH cells.