| First Author | Muro R | Year | 2022 |
| Journal | Front Immunol | Volume | 13 |
| Pages | 1045881 | PubMed ID | 36713401 |
| Mgi Jnum | J:355401 | Mgi Id | MGI:7431686 |
| Doi | 10.3389/fimmu.2022.1045881 | Citation | Muro R, et al. (2022) Spleen tyrosine kinase mediates the gammadeltaTCR signaling required for gammadeltaT cell commitment and gammadeltaT17 differentiation. Front Immunol 13:1045881 |
| abstractText | The gammadeltaT cells that produce IL-17 (gammadeltaT17 cells) play a key role in various pathophysiologic processes in host defense and homeostasis. The development of gammadeltaT cells in the thymus requires gammadeltaT cell receptor (gammadeltaTCR) signaling mediated by the spleen tyrosine kinase (Syk) family proteins, Syk and Zap70. Here, we show a critical role of Syk in the early phase of gammadeltaT cell development using mice deficient for Syk specifically in lymphoid lineage cells (Syk-conditional knockout (cKO) mice). The development of gammadeltaT cells in the Syk-cKO mice was arrested at the precursor stage where the expression of Rag genes and alphabetaT-lineage-associated genes were retained, indicating that Syk is required for gammadeltaT-cell lineage commitment. Loss of Syk in gammadeltaT cells weakened TCR signal-induced phosphorylation of Erk and Akt, which is mandatory for the thymic development of gammadeltaT17 cells. Syk-cKO mice exhibited a loss of gammadeltaT17 cells in the thymus as well as throughout the body, and thereby are protected from gammadeltaT17-dependent psoriasis-like skin inflammation. Collectively, our results indicate that Syk is a key player in the lineage commitment of gammadeltaT cells and the priming of gammadeltaT17 cell differentiation. |
