| First Author | Sanjo H | Year | 2015 |
| Journal | PLoS One | Volume | 10 |
| Issue | 7 | Pages | e0128761 |
| PubMed ID | 26132627 | Mgi Jnum | J:238318 |
| Mgi Id | MGI:5819030 | Doi | 10.1371/journal.pone.0128761 |
| Citation | Sanjo H, et al. (2015) Conditional Deletion of TAK1 in T Cells Reveals a Pivotal Role of TCRalphabeta+ Intraepithelial Lymphocytes in Preventing Lymphopenia-Associated Colitis. PLoS One 10(7):e0128761 |
| abstractText | 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 TCRalphabeta+CD8alpha+ intestinal intraepithelial lymphocytes (IELs) and this was largely due to the developmental defect of the thymic precursors by TAK1 deficiency. Remarkably, transfer of TCRalphabeta+CD8alpha+ IELs from wild-type mice ameliorated colitis in Lck-cre:TAK1fl/fl mice. Taken together, our current study highlighted the emerging role of TAK1 in configuring the gut-specialized T cell subset, which regulates mucosal homeostasis under lymphopenic conditions. |
