19:10 - 21:00
Room: Ishikawa Ongakudō Interchange Hall
Poster Session
Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis
Sayaka Ishihara1, Miho Mamiyoda1, Tsuyoshi Sato1, Akihiko Nishikimi1, Makoto Saegusa2, Koko Katagiri1
1Department of Biosciences, School of Science, Kitasato University, Sagamihara, Japan, 2Department of Pathology, School of Medicine, Kitasato University, Sagamihara, Japan

Rap1-GTP is necessary for leukocyte function-associated antigen-1 (LFA-1)-dependent arrest of naïve T cells on the high endothelial venule (HEV). Here we show that Rap1-GDP restrains rolling behaviours of T cells on the peripheral lymph node addressin by inhibiting tether formation. Consequently, Rap1 deficiency impairs homing of naive T cells to peripheral lymph nodes, which induces the differentiation of CD4+ T cells into Th17 cells in microbiota-dependent manner. On the other hand, Rap1 deficiency accelerates alpha4beta7-dependent homing of effector T cells such as Th17 and Th1 cells to the colon, resulting in spontaneous colitis with tumours. Rap1-GDP associates with and activates lymphocyte-oriented kinase, which phosphorylates ERM (ezrin, radixin and moesin) in resting T cells. Phosphomimetic ezrin reduces the rolling of Rap1-deficient cells, and thereby decreases their homing into the colon. On the other hand, chemokines activate Rap1 at the plasma membrane within seconds, and Rap1-GTP binds to filamins, which diminishes its association with the b2 chain of LFA-1 and results in LFA-1 activation. This Rap1-dependent regulation of T-cell circulation prevents the maturation of pathogenic Th17 cells in mesenteric lymph nodes and their trafficking into colon lamina propria, which are major contributing factors to the pathogenesis of colitis.


Reference:
Tu-P6-22
Session:
Poster Session 6 “Cytokines in mucosal immunity”
Presenter/s:
Sayaka Ishihara
Presentation type:
Poster Presentation
Room:
Ishikawa Ongakudō Interchange Hall
Date:
Tuesday, 31 October 2017
Time:
19:10 - 21:00
Session times:
19:10 - 21:00