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Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation
Author(s) -
Zarin Payam,
In Tracy SH,
Chen Edward LY,
Singh Jastaranpreet,
Wong Gladys W,
Mohtashami Mahmood,
Wiest David L,
Anderson Michele K,
ZúñigaPflücker Juan Carlos
Publication year - 2018
Publication title -
immunology and cell biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.999
H-Index - 104
eISSN - 1440-1711
pISSN - 0818-9641
DOI - 10.1111/imcb.12164
Subject(s) - microbiology and biotechnology , notch signaling pathway , biology , cytokine , t cell receptor , t cell , effector , stromal cell , receptor , immunology , signal transduction , cancer research , immune system , biochemistry
γδ 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‐γ ( IFN γ) and interleukin‐17 ( IL ‐17) producing γδ T‐cells remain unknown. Here, we define the cues involved in the functional programming of γδ T‐cells, by examining the roles of T‐cell receptor ( TCR ), Notch, and cytokine‐receptor signaling. KN 6 γδ TCR ‐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 IFN γ versus IL ‐17 producing γδ T‐cell subsets, with Notch and weak TCR ligands optimally enabling development of γδ17 cells in the presence of IL ‐1β, IL ‐21 and IL ‐23. Notably, these cytokines were also shown to be required for the intrathymic development of γδ17 cells. Together, this work provides a framework of how signals downstream of TCR , Notch and cytokine receptors integrate to program the effector function of IFN γ and IL ‐17 producing γδ T‐cell subsets.