AUTHOR=Muro Ryunosuke , Narita Tomoya , Nitta Takeshi , Takayanagi Hiroshi 

TITLE=Spleen tyrosine kinase mediates the γδTCR signaling required for γδT cell commitment and γδT17 differentiation

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.1045881

DOI=10.3389/fimmu.2022.1045881

ISSN=1664-3224

ABSTRACT=The gdT cells that produce IL-17 (gdT17 cells) play a key role in various pathophysiologic processes in host defense and homeostasis. The development of gdT cells in the thymus requires gdT cell receptor (gdTCR) 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 gdT cell development using mice deficient for Syk specifically in lymphoid lineage cells (Syk-conditional knockout (cKO) mice). The development of gdT cells in the Syk-cKO mice was arrested at the precursor stage where the expression of Rag genes and abT-lineage-associated genes were retained, indicating that Syk is required for gdT-cell lineage commitment. Loss of Syk in gdT cells weakened TCR signal-induced phosphorylation of Erk and Akt, which is mandatory for the thymic development of gdT17 cells. Syk-cKO mice exhibited a loss of gdT17 cells in the thymus as well as throughout the body, and thereby are protected from gdT17-dependent psoriasis-like skin inflammation. Collectively, our results indicate that Syk is a key player in the lineage commitment of gdT cells and the priming of gdT17 cell differentiation.