| First Author | Okamura K | Year | 2016 |
| Journal | Sci Rep | Volume | 6 |
| Pages | 36135 | PubMed ID | 27786304 |
| Mgi Jnum | J:254105 | Mgi Id | MGI:6101773 |
| Doi | 10.1038/srep36135 | Citation | Okamura K, et al. (2016) Survival of mature T cells depends on signaling through HOIP. Sci Rep 6:36135 |
| abstractText | T cell development in the thymus is controlled by a multistep process. The NF-kappaB pathway regulates T cell development as well as T cell activation at multiple differentiation stages. The linear ubiquitin chain assembly complex (LUBAC) is composed of Sharpin, HOIL-1L and HOIP, and it is crucial for regulating the NF-kappaB and cell death pathways. However, little is known about the roles of LUBAC in T-cell development and activation. Here, we show that in T-HOIP(Deltalinear) mice lacking the ubiquitin ligase activity of LUBAC, thymic CD4(+) or CD8(+) T cell numbers were markedly reduced with severe defects in NKT cell development. HOIP(Deltalinear) CD4(+) T cells failed to phosphorylate IkappaBalpha and JNK through T cell receptor-mediated stimulation. Mature CD4(+) and CD8(+) T cells in T-HOIP(Deltalinear) mice underwent apoptosis more rapidly than control T cells, and it was accompanied by lower CD127 expression on CD4(+)CD24(low) and CD8(+)CD24(low) T cells in the thymus. The enforced expression of CD127 in T-HOIP(Deltalinear) thymocytes rescued the development of mature CD8(+) T cells. Collectively, our results showed that LUBAC ligase activity is key for the survival of mature T cells, and suggest multiple roles of the NF-kappaB and cell death pathways in activating or maintaining T cell-mediated adaptive immune responses. |
