| First Author | Chen X | Year | 2022 |
| Journal | Sci Adv | Volume | 8 |
| Issue | 21 | Pages | eabm9120 |
| PubMed ID | 35613277 | Mgi Jnum | J:326393 |
| Mgi Id | MGI:7284560 | Doi | 10.1126/sciadv.abm9120 |
| Citation | Chen X, et al. (2022) Differential metabolic requirement governed by transcription factor c-Maf dictates innate gammadeltaT17 effector functionality in mice and humans. Sci Adv 8(21):eabm9120 |
| abstractText | Cellular metabolism has been proposed to govern distinct gammadelta T cell effector functions, but the underlying molecular mechanisms remain unclear. We show that interleukin-17 (IL-17)-producing gammadelta T (gammadeltaT17) and interferon-gamma (IFN-gamma)-producing gammadelta T (gammadeltaT1) 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 gammadeltaT17 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 gammadelta T cells. Deletion of c-Maf in gammadelta 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 gammadelta T cells from peripheral blood and in oral cancers. These results demonstrate a critical role of the transcription factor c-Maf in regulating gammadeltaT17 effector function through IDH2-mediated metabolic reprogramming. |
