| First Author | Köchl R | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 33051000 | Mgi Jnum | J:303541 |
| Mgi Id | MGI:6681934 | Doi | 10.7554/eLife.56934 |
| Citation | Kochl R, et al. (2020) Critical role of WNK1 in MYC-dependent early mouse thymocyte development. Elife 9:e56934 |
| abstractText | WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4(+) T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the beta-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development. |
