Gab2 and Gab3 Redundantly Suppress Colitis by Modulating Macrophage and CD8⁺ T-Cell Activation.

ABSTRACT: Inflammatory Bowel Disease (IBD) is a multi-factorial chronic inflammation of the gastrointestinal tract prognostically linked to CD8⁺ T-cells, but little is known about their mechanism of activation during initiation of colitis. Here, Grb2-associated binding 2/3 adaptor protein double knockout mice (Gab2/3^-/-) were generated. Gab2/3^-/- mice, but not single knockout mice, developed spontaneous colitis. To analyze the cellular mechanism, reciprocal bone marrow (BM) transplantation demonstrated a Gab2/3^-/- hematopoietic disease-initiating process. Adoptive transfer showed individual roles for macrophages and T-cells in promoting colitis development in vivo. In spontaneous disease, intestinal intraepithelial CD8⁺ but much fewer CD4

SUBMITTER: Wang Z 

PROVIDER: S-EPMC6431666 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature