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 costimulatory molecule ICOS is important for the development of both interleukin 17–producing and follicular T helper cells. Kuchroo and colleagues find that ICOS induces the transcription factor c-Maf, which regulates the population expansion of both helper cell types. 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 T FH cells. We also show that T FH cells produced IL-17 and that T FH cells in ICOS-deficient mice were defective in IL-17 production. Both T H -17 and T FH 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.