ICOS signal facilitates Foxp3 transcription to favor suppressive function of regulatory T cells.

Inducible costimulator (ICOS) plays an important role in the suppressive immunity mediated by regulatory T cells (Tregs), but the molecular regulation mechanism is not well known. Here we performed a study to explore the possible mechanism by which ICOS regulates the suppressive functions and survival of Tregs. This study showed that both the ICOS and CD28 signal could promote the survival of Tregs. However, ICOS but not CD28 improved the suppressive function of Tregs. Mechanistic studies demonstrated that ICOS could induce the transcription activity of Foxp3, by facilitating the nuclear factor of activated T cells (NFAT): Foxp3 over NFAT: activator protein 1 (AP-1). The results of Q-PCR showed that AP1 downstream regulatory genes (IL-2 and IL-6) were down-regulated, and Foxp3 downstream regulatory genes (IL-4, IL-10 and TGF-β) were up-regulated. Further, ICOS promoted anti-apoptosis may be by activating protein kinase B (Akt) signal. These findings demonstrated that ICOS signal could facilitate Foxp3 transcription in favor of survival and suppressive function of Tregs.