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TAK1 is indispensable for development of T cells and prevention of colitis by the generation of regulatory T cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Sato, Shintaro Sanjo, Hideki Tsujimura, Tohru Ninomiya-Tsuji, Jun Yamamoto, Masahiro Kawai, Taro Takeuchi, Osamu Akira, Shizuo |
| Copyright Year | 2006 |
| Abstract | Transforming growth factor (TGF)-beta-activating kinase 1 (TAK1) is critical for Toll-like receptor- and tumor necrosis factor-mediated cellular responses. In B cells, TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs), but not nuclear factor-kappaB (NF-kappaB), in antigen receptor signaling. In this study, we generate T cell-specific TAK1-deficient (Lck(Cre/(+))Tak1(flox/flox)) mice and show that TAK1 is indispensable for the maintenance of peripheral CD4 and CD8 T cells. In thymocytes, TAK1 is essential for TCR-mediated activation of both NF-kappaB and MAPKs. Additionally, Lck(Cre/(+))Tak1(flox/flox) mice developed colitis as they aged. In these mice, accumulations of activated/memory T cells as well as B cells were observed. Development of regulatory T (Treg) cells in thymus was abrogated in Lck(Cre/(+))Tak1(flox/flox) mice, suggesting that the loss of Treg cells is the cause of the disease. Together, the results show that TAK1, by controlling the generation of central Treg cells, is important for preventing spontaneously developing colitis. |
| Starting Page | 297 |
| Ending Page | 306 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://oup.silverchair-cdn.com/oup/backfile/Content_public/Journal/intimm/18/10/10.1093/intimm/dxl082/2/dxl082.pdf?Expires=1491413618&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q&Signature=ePSu-xcqEzl3eH3zqP~r-qItfYTvGxWUc4n5XrEErjU~2-jJ2sOz0sBaPmTtoMrNUcD7RNBS2zNZi1AsRjf32ryA6quwmp7Au9JwVjW29bnw6MOXmSwP0ZY1bwII2QtoN6J4hpBZrab7u4jBTtUpBU2tzeDrnpaPCJEPbQPuTFjV4XW3BUzaT3lkv3mNN0BkY8Ck-uMz~nGOJ9YEzaiedYIE2c-7QvfnpX~Oe1cU2nxY9-6cL2Z0R3K4ZieMo1ONxUVf-jD6aixSAdKjhTUnCGCcJlZXBLnypE1TSVl~U04avLLNz5m45r5ty9rCwVKoKDc51y4J0j0IfwED35L1jQ__ |
| PubMed reference number | 16940043v1 |
| Volume Number | 18 |
| Issue Number | 10 |
| Journal | International immunology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Colitis F Factor Leukemia, B-Cell MAP3K7 wt Allele Mitogen-Activated Protein Kinases Mitogens NF-kappa B NR2C2 wt Allele Necrosis Neoplasms Receptors, Antigen T-Cell Receptor TLR4 protein, human Thymic Tissue thymocyte |
| Content Type | Text |
| Resource Type | Article |
