| First Author | Muro R | Year | 2018 |
| Journal | J Clin Invest | Volume | 128 |
| Issue | 1 | Pages | 415-426 |
| PubMed ID | 29202478 | Mgi Jnum | J:258367 |
| Mgi Id | MGI:6117967 | Doi | 10.1172/JCI95837 |
| Citation | Muro R, et al. (2018) gammadeltaTCR recruits the Syk/PI3K axis to drive proinflammatory differentiation program. J Clin Invest 128(1):415-426 |
| abstractText | gammadeltaT cells produce inflammatory cytokines and have been implicated in the pathogenesis of cancer, infectious diseases, and autoimmunity. The T cell receptor (TCR) signal transduction that specifically regulates the development of IL-17-producing gammadeltaT (gammadeltaT17) cells largely remains unclear. Here, we showed that the receptor proximal tyrosine kinase Syk is essential for gammadeltaTCR signal transduction and development of gammadeltaT17 in the mouse thymus. Zap70, another tyrosine kinase essential for the development of alphabetaT cells, failed to functionally substitute for Syk in the development of gammadeltaT17. Syk induced the activation of the PI3K/Akt pathway upon gammadeltaTCR stimulation. Mice deficient in PI3K signaling exhibited a complete loss of gammadeltaT17, without impaired development of IFN-gamma-producing gammadeltaT cells. Moreover, gammadeltaT17-dependent skin inflammation was ameliorated in mice deficient in RhoH, an adaptor known to recruit Syk. Thus, we deciphered lineage-specific TCR signaling and identified the Syk/PI3K pathway as a critical determinant of proinflammatory gammadeltaT cell differentiation. |
