Integration of T‐cell receptor, Notch and cytokine signals programs mouse γδ T‐cell effector differentiation
| Autor: | Mahmood Mohtashami, Juan Carlos Zúñiga-Pflücker, Edward L. Y. Chen, David L. Wiest, Gladys W. Wong, Michele K. Anderson, Jastaranpreet Singh, Tracy Sh In, Payam Zarin |
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| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
T‐cell receptor Stromal cell Notch medicine.medical_treatment T cell T-Lymphocytes Immunology Biology Lymphocyte Activation Interferon-gamma 03 medical and health sciences Mice 0302 clinical medicine medicine Immunology and Allergy Animals Progenitor cell Receptor Mice Inbred BALB C Receptors Notch Effector T-cell receptor Interleukin-17 Cell Differentiation Receptors Antigen T-Cell gamma-delta Cell Biology Original Articles Cell biology Mice Inbred C57BL 030104 developmental biology Cytokine medicine.anatomical_structure Cytokines Original Article Function (biology) Signal Transduction 030215 immunology |
| Zdroj: | Immunology and Cell Biology |
| ISSN: | 1440-1711 0818-9641 |
| Popis: | 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 (IFNγ) 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. KN6 γδTCR‐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 IFNγ 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 IFNγ and IL‐17 producing γδ T‐cell subsets. |
| Databáze: | OpenAIRE |
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