| First Author | Gruber LC | Year | 2023 |
| Journal | Eur J Immunol | Volume | 53 |
| Issue | 1 | Pages | e2250017 |
| PubMed ID | 36401605 | Mgi Jnum | J:333873 |
| Mgi Id | MGI:7442748 | Doi | 10.1002/eji.202250017 |
| Citation | Gruber LC, et al. (2023) Knockout of SLy1 decreases double-negative thymocyte proliferation and protects mice from p53-induced tumor formation. Eur J Immunol 53(1):e2250017 |
| abstractText | The lymphocyte-specific adapter protein SLy1 has previously been identified as indispensable for thymocyte development and T-cell proliferation and, recently, as a cause of X-linked combined immunodeficiency in humans that recapitulates many of the abnormalities reported in SLy1(KO) and SLy1(d/d) mice. As SLy1(KO) NK cells show increased levels of p53, we focused our research on the interdependency of SLy1 and p53 for thymocyte development. Using RT-PCR and immunoblot analysis, we observed increased levels of p53 as well as DNA damage response proteins in SLy1(KO) thymocytes. To test for rescue from SLy1-induced deficiencies in thymocyte development like reduced thymocyte numbers and reduced DN to DP progression, we generated a mouse model with T cell-specific p53-deficiency on an SLy1(KO) background and analyzed lymphocyte populations in these mice and respective controls. Astonishingly, SLy1(KO) -typical deficiencies were retained, showing that SLy1 is mechanistically independent of p53. Studies of apoptosis and proliferation in SLy1KO thymocytes revealed decreased proliferation in the DN3 subpopulation as a possible reason for the decreased thymocyte number. In mice with p53-deficient T cells, we observed tumor formation leading to reduced survival, preferentially in SLy1(WT) mice. Thus, we suggest that a SLy1-deficiency reduces proliferation, resulting in less hematologic tumors initiated by the p53-deficiency. |
