Rap1 prevents colitogenic Th17 cell expansion and facilitates Treg cell differentiation and distal TCR signaling

• DOI: 10.1038/s42003-022-03129-x
• Publication Date: 2022-03-04T13:36:37Z
• Authors: Sayaka Ishihara; Tsuyoshi Sato; Noriyuki Fujikado; Haruka Miyazaki; Takayuki Yoshimoto; Hiromitsu Yamamoto; Shinji Fukuda; Koko Katagiri
• Keywords: CD86; CD80; NFAT; Rap1; RELB

Abstract T-cell-specific Rap1 deletion causes spontaneous colitis in mice. In the present study, we revealed that deficiency T cells impaired preceding induction of intestinal RORγt + Treg cells. large lamina propria (LILP) Rap1-knockout mice (Rap1KO mice), Th17 were found to increase a microbiota-dependent manner, and inhibition IL-17A production prevented development colitis. LILP Rap1KO mice, scarcely induced by 4 weeks age. The expression CTLA-4 on Rap1-deficient was reduced CD80 CD86 dendritic consequently elevated When cultured under each polarizing condition, naïve CD4 did not show biased differentiation into cells; their as well Th1 Th2 lesser than wild-type exhibit defective nuclear translocation NFAT formation actin foci response TCR engagement. These data suggest amplifies signaling required for Treg-mediated control colitogenic responses.