DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

Haiyan Zhou (), Xinyi Peng, Jie Hu, Liwen Wang, Hairong Luo, Junyan Zhang, Yacheng Zhang, Guobao Li, Yujiao Ji, Jingjing Zhang, Juli Bai, Meilian Liu, Zhiguang Zhou and Feng Liu ()
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Haiyan Zhou: The Second Xiangya Hospital of Central South University
Xinyi Peng: The Second Xiangya Hospital of Central South University
Jie Hu: The Second Xiangya Hospital of Central South University
Liwen Wang: The Second Xiangya Hospital of Central South University
Hairong Luo: The Second Xiangya Hospital of Central South University
Junyan Zhang: The Second Xiangya Hospital of Central South University
Yacheng Zhang: The Second Xiangya Hospital of Central South University
Guobao Li: The Second Xiangya Hospital of Central South University
Yujiao Ji: The Second Xiangya Hospital of Central South University
Jingjing Zhang: The Second Xiangya Hospital of Central South University
Juli Bai: University of Texas Health Science Center at San Antonio
Meilian Liu: University of New Mexico Health Sciences Center
Zhiguang Zhou: The Second Xiangya Hospital of Central South University
Feng Liu: The Second Xiangya Hospital of Central South University

Nature Communications, 2021, vol. 12, issue 1, 1-14

Abstract: Abstract Adipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

Date: 2021
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DOI: 10.1038/s41467-020-20665-4

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