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

37 Pages Posted: 26 Feb 2019 Publication Status: Published

See all articles by Yihua Cai

Yihua Cai

University of Louisville - Department of Medicine; University of Louisville - Department of Microbiology and Immunology

Feng Xue

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Hui Qin

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Na Liu

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Xu Chen

University of Louisville - Department of Medicine; University of Louisville - Department of Microbiology and Immunology

Chris Fleming

University of Louisville - Department of Medicine; University of Louisville - Department of Microbiology and Immunology

Xiaoling Hu

University of Louisville - Department of Medicine; University of Louisville - Department of Microbiology and Immunology

Huang-ge Zhang

University of Louisville - Department of Medicine; University of Louisville - Department of Microbiology and Immunology

Jie Zheng

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Jun Yan

University of Louisville - Department of Medicine; University of Louisville - Department of Microbiology and Immunology

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Abstract

Innate dermal γδ T cells play a critical role in skin homeostasis and inflammation. However, the underlying molecular mechanisms by which these cells are activated and differentiated have not been fully understood. In this study, we show that the mTOR signaling and STAT3 pathways are activated in dermal γδ T cells in response to innate stimuli such as IL-1β and IL-23. Although both mTOC1 and mTOC2 are essential for dermal γδ T cell proliferation, mTOC2 deficiency leads to drastically decreased dermal γδT17 cells. Further studies reveal that the IL-1R-MyD88- mTOR pathway is critical in dermal γδ T cell effector function. It appears that mitochondriamediated oxidative phosphorylation is critical in this process. The absence of mTOC2 in dermal γδ T cells ameliorate skin inflammation in an Imiquimod-induced psoriasis-like model. Interestingly, STAT3 pathway while is critical in dermal Vγ4T17 cell effector function but is not required for dermal Vγ6T17 cells. In addition, transcription factor IRF-4 activation promotes dermal γδ T cell IL-17 production by linking IL-1β and IL-23 signaling. Taken together, our results demonstrate that the mTOR-STAT3 signaling differentially regulates dermal γδ T cell effector function in skin inflammation.

Suggested Citation

Cai, Yihua and Xue, Feng and Qin, Hui and Liu, Na and Chen, Xu and Fleming, Chris and Hu, Xiaoling and Zhang, Huang-ge and Zheng, Jie and Yan, Jun, Differential Roles of the mTOR-STAT3 Signaling in Dermal γδ T Cell Effector Function in Skin Inflammation (December 12, 2018). Available at SSRN: https://ssrn.com/abstract=3300040 or http://dx.doi.org/10.2139/ssrn.3300040
This version of the paper has not been formally peer reviewed.

Yihua Cai (Contact Author)

University of Louisville - Department of Medicine

Louisville, KY 40292
United States

University of Louisville - Department of Microbiology and Immunology

Louisville, KY 40292
United States

Feng Xue

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Shanghai 200030
China

Hui Qin

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Shanghai 200030
China

Na Liu

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Shanghai 200030
China

Xu Chen

University of Louisville - Department of Medicine

Louisville, KY 40292
United States

University of Louisville - Department of Microbiology and Immunology

Louisville, KY 40292
United States

Chris Fleming

University of Louisville - Department of Medicine

Louisville, KY 40292
United States

University of Louisville - Department of Microbiology and Immunology

Louisville, KY 40292
United States

Xiaoling Hu

University of Louisville - Department of Medicine

Louisville, KY 40292
United States

University of Louisville - Department of Microbiology and Immunology

Louisville, KY 40292
United States

Huang-ge Zhang

University of Louisville - Department of Medicine

Louisville, KY 40292
United States

University of Louisville - Department of Microbiology and Immunology

Louisville, KY 40292
United States

Jie Zheng

Shanghai Jiao Tong University (SJTU) - Department of Dermatology

Shanghai 200030
China

Jun Yan

University of Louisville - Department of Medicine

Louisville, KY 40292
United States

University of Louisville - Department of Microbiology and Immunology

Louisville, KY 40292
United States

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