Costimulatory molecule ICOS plays a critical role in the development of TH-17 and follicular T-helper cells by regulating c-Maf expression and IL-21 production

摘要

The inducible costimulatory molecule (ICOS) has been suggested to play an important role in the development of interleukin 17 (IL-17)-producing T helper cells (TH-17 cells) and of follicular helper cells (TFH cells), specialized helper T cells (CD4⁺CXCR5⁺ICOS^high) required for antibody class switching and germinal center formation. Here we show that ICOS, while not essential for the differentiation of TH-17 cells, was critical for maintaining effector-memory TH-17 cells as ICOS-deficient mice demonstrated a defect in the expansion of TH-17 cells after IL-23 stimulation. In addition, we found that TFH cells produced IL-17 and that ICOS-deficient mice demonstrated a reduced frequency of TFH with a defect in IL-17 production. Both TH-17 and TFH cells showed increased expression of the transcription factor c-Maf—normally associated with TH2 cells— and that loss of c-Maf results in a defect in IL-21 production, and consequently a defect in the maintenance of IL-23R expression and expansion of TH-17 and TFH cells. These data suggest that c-Maf induced by ICOS regulates IL-21 production that, in turn, regulates expansion of TH-17 cells and TFH cells.