Roles of mTORC1 and mTORC2 in controlling γδ T1 and γδ T17 differentiation and function

Yang, Qian; Liu, Xia; Liu, Qihui; Guan, Zerong; Luo, Jing; Cao, Guangchao; Cai, Ruitian; Li, Zhenhua; Xu, Yan; Wu, Zengfeng; Xu, Miaomiao; Zhang, Song; Zhang, Fan; Yang, Hengwen; Lin, Xue; Yang, Meixiang; Wu, Yangzhe; Gao, Yunfei; Flavell, Richard A.; Hao, Jianlei; Yin, Zhinan

doi:10.1038/s41418-020-0500-9

Cited by 38 publications

(42 citation statements)

References 34 publications

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“…Mouse naive splenic CD4 + T cells were prepared using the Naive CD4 + T Cell Isolation Kit (STEM-CELL Technologies). Mouse naive γδ T cells were isolated as previously described (62). The purity of the enriched subset was validated by flow cytometry and was generally higher than 95%.…”

Section: Discussionmentioning

confidence: 99%

GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis

Xia¹,

Cao²,

Sun³

et al. 2020

Journal of Clinical Investigation

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Section: Discussionmentioning

confidence: 99%

GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis

Xia¹,

Cao²,

Sun³

et al. 2020

Journal of Clinical Investigation

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“…( A ) In the normal cells, p73 promotes the IL6 production [ 144 ], which can have either pro- [ 187 , 188 ], or anti- cancerogenic effects by inducing Th17 v.s. Treg polarization [ 189 , 190 ]. In skin tissues, p73 regulates TSLR [ 151 ] that induces Th2 cell differentiation, thereby promoting chronic inflammation in atopic dermatitis and is associated with poor prognosis in several cancers [ 157 ].…”

Section: Figurementioning

confidence: 99%

Dual Role of p73 in Cancer Microenvironment and DNA Damage Response

Rozenberg

Zvereva

Dalina

et al. 2021

Cells

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Understanding the mechanisms that regulate cancer progression is pivotal for the development of new therapies. Although p53 is mutated in half of human cancers, its family member p73 is not. At the same time, isoforms of p73 are often overexpressed in cancers and p73 can overtake many p53 functions to kill abnormal cells. According to the latest studies, while p73 represses epithelial–mesenchymal transition and metastasis, it can also promote tumour growth by modulating crosstalk between cancer and immune cells in the tumor microenvironment, M2 macrophage polarisation, Th2 T-cell differentiation, and angiogenesis. Thus, p73 likely plays a dual role as a tumor suppressor by regulating apoptosis in response to genotoxic stress or as an oncoprotein by promoting the immunosuppressive environment and immune cell differentiation.

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“…Moreover, both flow cytometry analysis and capillary western blot illustrated the expression of phospho-AKT and phospho-mTOR was downregulated in gd T cells after culture with Dmannose (Figures 6E, F and Figure S7). Together, considering the crucial roles of AKT/mTOR signaling in glycolysis (35,37), our results suggested that D-mannose treatment contributed to the lower proliferation and higher apoptosis of gd T cells by impairing glycolysis via the AKT/mTOR axis.…”

Section: D-mannose Suppressed the Proliferation And Il-17 Production ...mentioning

confidence: 59%

“…AKT/mTOR signaling participates in the progression of psoriasis and tunes the fate of T cell by HIF-1a-mediated glycolysis (46)(47)(48). mTOR1 is required for the proliferation and survival of peripheral Vg4 + gd T cells, while mTOR1 and mTOR2 potentiate gd17 T cells by regulating glycolysis and mitochondrial ROS production (35). Hence, the prevention of glycolysis via downregulation of AKT/ mTOR signaling may explain the suppression of gd T cells' proliferation and survival by D-mannose.…”

Section: Discussionmentioning

confidence: 99%

D-Mannose Suppresses γδ T Cells and Alleviates Murine Psoriasis

Cheng

Tian

et al. 2022

Front. Immunol.

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Psoriasis is a chronic skin disorder associated with multiple sequelae, such as psoriatic arthritis and cardiovascular diseases. Increasing evidence has shown that γδ T cells, as sources of IL-17A, play critical roles in psoriatic inflammations. However, there still lack effective ways to manipulate these pathogenic γδ T cells, which are less well studied than αβ T cells. The present study aims to characterize the phenotype of γδ T cells and evaluate the impact of D-mannose (a C-2 epimer of glucose) on γδ T cell-mediated psoriasis. We found that skin-draining LN γδ T cells underwent robust proliferation and acquired an IL-17-producing phenotype during psoriasis. The transcriptomic profiles of these psoriatic γδ T cells had elevated glycolytic signatures. Importantly, D-mannose treatment suppressed the γδ T cell reaction and successfully alleviated the local and systematic inflammation induced by imiquimod. The decreased AKT/mTOR/HIF-1α signaling and glycolytic ability may contribute to the suppression of γδ T cells achieved by D-mannose. Our study increased understanding of γδ T cells in psoriasis and promoted D-mannose utilization as a potential clinical application for autoimmune diseases driven by γδ T cells.

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Roles of mTORC1 and mTORC2 in controlling γδ T1 and γδ T17 differentiation and function

Cited by 38 publications

References 34 publications

GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis

GLS1-mediated glutaminolysis unbridled by MALT1 protease promotes psoriasis pathogenesis

Dual Role of p73 in Cancer Microenvironment and DNA Damage Response

D-Mannose Suppresses γδ T Cells and Alleviates Murine Psoriasis

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