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Zarin P , In TS , Chen EL , Singh J , Wong GW , Mohtashami M , Wiest DL , Anderson MK , Zuniga-Pflucker JC
Integration of T Cell Receptor, Notch and Cytokine Signals Programs in Mouse gammadelta T Cell Effector Differentiation
Immunol Cell Biol. 2018 Oct;96(9) :994-1007
PMID: 29754419 PMCID: PMC6197911 URL: https://www.ncbi.nlm.nih.gov/pubmed/29754419
Abstractgammadelta T-cells perform a wide range of tissue and disease specific functions that are dependent on the effector cytokines produced by these cells. However, the aggregate signals required for the development of interferon-gamma (IFNgamma) and interleukin-17 (IL-17) producing gammadelta T-cells remain unknown. Here, we define the cues involved in the functional programming of gammadelta T-cells, by examining the roles of T-cell receptor (TCR), Notch, and cytokine-receptor signaling. KN6 gammadeltaTCR-transduced Rag2(-/-) T-cell progenitors were cultured on stromal cells variably expressing TCR and Notch ligands, supplemented with different cytokines. We found that distinct combinations of these signals are required to program IFNgamma versus IL-17 producing gammadelta T cell subsets, with Notch and weak TCR ligands optimally enabling development of gammadelta17 cells in the presence of IL-1beta, IL-21 and IL-23. Notably, these cytokines were also shown to be required for the intrathymic development of gammadelta17 cells. Together, this work provides a framework of how signals downstream of TCR, Notch and cytokine receptors integrate to program the effector function of IFNgamma and IL-17 producing gammadelta T-cell subsets. This article is protected by copyright. All rights reserved.
Notes1440-1711 Zarin, Payam In, Tracy S H Chen, Edward L Y Singh, Jastaranpreet Wong, Gladys W Mohtashami, Mahmood Wiest, David L Anderson, Michele K Zuniga-Pflucker, Juan Carlos Journal Article England Immunol Cell Biol. 2018 May 13. doi: 10.1111/imcb.12164.