Regulatory T (Treg) cells, in which Foxp3 is the master regulator, play central roles in maintaining immune homeostasis and self-tolerance. However, the regulation mechanism underlying Treg cell homeostasis and function still remains unclear. Here, we report that another Foxp family protein, Foxp1, is required for the maintenance of Treg cell quiescence and suppressor function. Specific deletion of Foxp1 in Treg cells resulted in more activated Treg cells in mice, but impaired Treg cell function. Mice with Foxp1-deficient Treg cells gradually developed spontaneous inflammatory disease with age. In addition, these mice exhibited much more severe inflammatory diseases both in DSS induced colitis and EAE models. Mechanistically, we found that Foxp1 helped maintain Treg cell suppressive function by stabilizing Foxp3 expression. Further, we identified CTLA-4 as a direct target of Foxp1 in Treg cells. Foxp1 cooperated with Foxp3 in the optimal regulation of CTLA-4 expression. Thus, our studies revealed the critical functions of Foxp1 in regulating Treg cell homeostasis and suppressive function. SOURCE: Jinyi Tang (taotao11011011@163.com) - Wang Haikun IPS

Pluto Bioinformatics

GSE121251: Foxp1 is critical for the maintenance of Treg cell quiescence and suppressive function