| First Author | Song Y | Year | 2015 |
| Journal | Immunology | Volume | 144 |
| Issue | 2 | Pages | 245-53 |
| PubMed ID | 25074726 | Mgi Jnum | J:220126 |
| Mgi Id | MGI:5632263 | Doi | 10.1111/imm.12365 |
| Citation | Song Y, et al. (2015) c-Met signalling is required for efficient postnatal thymic regeneration and repair. Immunology 144(2):245-53 |
| abstractText | We have reported that in vivo administration of the hybrid cytokine rIL-7/HGFbeta or rIL-7/HGFalpha, which contains interleukin-7 (IL-7) and the beta- or alpha-chain of hepatocyte growth factor (HGF), significantly enhances thymopoiesis in mice after bone marrow transplantation. We have shown that the HGF receptor, c-Met, is involved in the effect of the hybrid cytokines. To address the role of c-Met signalling in thymocyte development and recovery, we generated conditional knockout (cKO) mice in which c-Met was specifically deleted in T cells by crossing c-Met(ft/ft) mice with CD4-Cre transgenic mice. We show here that although the number of total thymocytes and thymocyte subsets in young c-Met cKO mice is comparable to age-matched control (Ctrl) mice, the cKO mice were more susceptible to sub-lethal irradiation and dexamethasone treatment. This was demonstrated by low recovery in thymic cellularity in c-Met cKO mice after insult. Furthermore, the number of total thymocytes and thymocyte subsets was markedly reduced in 6- to 12-month-old cKO mice compared with age-matched Ctrl mice, and the thymic architecture of 12-month-old cKO mice was similar to that of 20-month-old wild-type mice. In addition, c-Met deficiency reduced cell survival and the expression of Bcl-xL in double-positive thymocytes, and decreased cell proliferation and the expression of cyclin E and cyclin-dependent kinase 5 in single-positive thymocytes. Our data indicate that c-Met signalling plays an important role in thymic regeneration after thymic insult. In addition, T-cell-specific inactivation of c-Met accelerates age-related thymic involution. |
