Conditional Deletion of TAK1 in T Cells Reveals a Pivotal Role of TCRαβ+ Intraepithelial Lymphocytes in Preventing Lymphopenia-Associated Colitis.

ABSTRACT: The kinase TAK is required for the development of conventional and regulatory T cells. We previously reported that mice with conditional deletion of TAK1 in T cells (Lck-cre:TAK1fl/fl mice) exhibited severe T lymphopenia, and were nevertheless predisposed to spontaneous colitis with unknown etiology. Here we focused on the immunopathological mechanism in colitic Lck-cre:TAK1fl/fl mice. We found that 'leaky' CD4+ T cells retaining TAK1 acquired inflammatory phenotypes that contribute to disease onset in Lck-cre:TAK1fl/fl mice. Furthermore, the gut microbiota-triggered signaling was also a key event leading to the pathogenesis. We discovered that Lck-cre:TAK1fl/fl mice were almost completely devoid of TCRαβ+CD8α+ intestinal intraepithelial lymphocytes (IELs) and this was largely due to the d

SUBMITTER: Sanjo H 

PROVIDER: S-EPMC4489433 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature