| First Author | Cai Y | Year | 2019 |
| Journal | Cell Rep | Volume | 27 |
| Issue | 10 | Pages | 3034-3048.e5 |
| PubMed ID | 31167146 | Mgi Jnum | J:284459 |
| Mgi Id | MGI:6381261 | Doi | 10.1016/j.celrep.2019.05.019 |
| Citation | Cai Y, et al. (2019) Differential Roles of the mTOR-STAT3 Signaling in Dermal gammadelta T Cell Effector Function in Skin Inflammation. Cell Rep 27(10):3034-3048.e5 |
| abstractText | Dermal gammadeltaT cells play critical roles in skin homeostasis and inflammation. However, the underlying molecular mechanisms by which these cells are activated have not been fully understood. Here, we show that the mechanistic or mammalian target of rapamycin (mTOR) and STAT3 pathways are activated in dermal gammadeltaT cells in response to innate stimuli such as interleukin-1beta (IL-1beta) and IL-23. Although both mTOR complex 1 (mTORC1) and mTORC2 are essential for dermal gammadeltaT cell proliferation, mTORC2 deficiency leads to decreased dermal gammadeltaT17 cells. It appears that mitochondria-mediated oxidative phosphorylation is critical in this process. Notably, although the STAT3 pathway is critical for dermal Vgamma4T17 effector function, it is not required for Vgamma6T17 cells. Transcription factor IRF-4 activation promotes dermal gammadeltaT cell IL-17 production by linking IL-1beta and IL-23 signaling. The absence of mTORC2 in dermal gammadeltaT cells, but not STAT3, ameliorates skin inflammation. Taken together, our results demonstrate that the mTOR-STAT3 signaling differentially regulates dermal gammadeltaT cell effector function in skin inflammation. |
