c-Met signalling is required for efficient postnatal thymic regeneration and repair
| Autor: | Pranau Panchatsharam, Yinhong Song, Laijun Lai, Min Su, Debra Rood |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
CD4-Positive T-Lymphocytes
Genetically modified mouse medicine.medical_specialty Cyclin E C-Met Cell Survival medicine.medical_treatment Immunology Anti-Inflammatory Agents bcl-X Protein Thymus Gland CD8-Positive T-Lymphocytes Biology Dexamethasone Mice chemistry.chemical_compound T-Lymphocyte Subsets Internal medicine Conditional gene knockout medicine Animals Regeneration Immunology and Allergy Cell Proliferation Mice Knockout Thymic involution Thymocytes Cell Differentiation Cyclin-Dependent Kinase 5 Original Articles Proto-Oncogene Proteins c-met CD4 Lymphocyte Count Cell biology Mice Inbred C57BL Thymocyte Cytokine Endocrinology chemistry Hepatocyte growth factor Signal Transduction medicine.drug |
| Zdroj: | Immunology. 144:245-253 |
| ISSN: | 0019-2805 |
| Popis: | We have reported that in vivo administration of the hybrid cytokine rIL-7/HGFβ or rIL-7/HGFα, which contains interleukin-7 (IL-7) and the β- or α-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. |
| Databáze: | OpenAIRE |
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