Conditional Deletion of TAK1 in T Cells Reveals a Pivotal Role of TCRαß+ Intraepithelial Lymphocytes in Preventing Lymphopenia-Associated Colitis.
PLoS One
; 10(7): e0128761, 2015.
Article
in En
| MEDLINE
| ID: mdl-26132627
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-creTAK1fl/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-creTAK1fl/fl mice. We found that 'leaky' CD4+ T cells retaining TAK1 acquired inflammatory phenotypes that contribute to disease onset in Lck-creTAK1fl/fl mice. Furthermore, the gut microbiota-triggered signaling was also a key event leading to the pathogenesis. We discovered that Lck-creTAK1fl/fl mice were almost completely devoid of TCRαß+CD8α+ intestinal intraepithelial lymphocytes (IELs) and this was largely due to the developmental defect of the thymic precursors by TAK1 deficiency. Remarkably, transfer of TCRαß+CD8α+ IELs from wild-type mice ameliorated colitis in Lck-creTAK1fl/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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
T-Lymphocyte Subsets
/
Receptors, Antigen, T-Cell, alpha-beta
/
Colitis
/
MAP Kinase Kinase Kinases
/
Intestinal Mucosa
/
Lymphopenia
Type of study:
Risk_factors_studies
Limits:
Animals
Language:
En
Journal:
PLoS One
Journal subject:
CIENCIA
/
MEDICINA
Year:
2015
Document type:
Article
Affiliation country:
Japón