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Differential Roles of the mTOR-STAT3 Signaling in Dermal γδ T Cell Effector Function in Skin Inflammation.

Yihua Cai | Feng Xue | Hui Qin | Xu Chen | Na Liu | Chris Fleming | Xiaoling Hu | Huang-Ge Zhang | Fuxiang Chen | Jie Zheng | Jun Yan
Cell reports | 2019

Dermal γδT 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 γδT cells in response to innate stimuli such as interleukin-1β (IL-1β) and IL-23. Although both mTOR complex 1 (mTORC1) and mTORC2 are essential for dermal γδT cell proliferation, mTORC2 deficiency leads to decreased dermal γδT17 cells. It appears that mitochondria-mediated oxidative phosphorylation is critical in this process. Notably, although the STAT3 pathway is critical for dermal Vγ4T17 effector function, it is not required for Vγ6T17 cells. Transcription factor IRF-4 activation promotes dermal γδT cell IL-17 production by linking IL-1β and IL-23 signaling. The absence of mTORC2 in dermal γδT cells, but not STAT3, ameliorates skin inflammation. Taken together, our results demonstrate that the mTOR-STAT3 signaling differentially regulates dermal γδT cell effector function in skin inflammation.

Pubmed ID: 31167146

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI128818

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

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