Differential metabolic requirement governed by transcription factor c-Maf dictates innate γδT17 effector functionality in mice and humans.
In: Science advances, Jg. 8 (2022-05-27), Heft 21, S. eabm9120
Online
academicJournal
Zugriff:
Cellular metabolism has been proposed to govern distinct γδ T cell effector functions, but the underlying molecular mechanisms remain unclear. We show that interleukin-17 (IL-17)-producing γδ T (γδT17) and interferon-γ (IFN-γ)-producing γδ T (γδT1) cells have differential metabolic requirements and that the rate-limiting enzyme isocitrate dehydrogenase 2 (IDH2) acts as a metabolic checkpoint for their effector functions. Intriguingly, the transcription factor c-Maf regulates γδT17 effector function through direct regulation of IDH2 promoter activity. Moreover, mTORC2 affects the expression of c-Maf and IDH2 and subsequent IL-17 production in γδ T cells. Deletion of c-Maf in γδ T cells reduces metastatic lung cancer development, suggesting c-Maf as a potential target for cancer immune therapy. We show that c-Maf also controls IL-17 production in human γδ T cells from peripheral blood and in oral cancers. These results demonstrate a critical role of the transcription factor c-Maf in regulating γδT17 effector function through IDH2-mediated metabolic reprogramming.
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Differential metabolic requirement governed by transcription factor c-Maf dictates innate γδT17 effector functionality in mice and humans.
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| Autor/in / Beteiligte Person: | Chen, X ; Cai, Y ; Hu, X ; Ding, C ; He, L ; Zhang, X ; Chen, F ; Yan, J |
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| Zeitschrift: | Science advances, Jg. 8 (2022-05-27), Heft 21, S. eabm9120 |
| Veröffentlichung: | Washington, DC : American Association for the Advancement of Science, [2015]-, 2022 |
| Medientyp: | academicJournal |
| ISSN: | 2375-2548 (electronic) |
| DOI: | 10.1126/sciadv.abm9120 |
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