Abstract: Objective To investigate the role of mucosal-associated invariant T (MAIT) cells in the regulatory mechanism of adipose browning. Methods A mouse model with functional deficiency of MAIT cells was established for comparison with the wild-type mice for levels of brown adipose tissue markers in response to cold stimulation using Western blotting and RT-PCR. Flow cytometry was used to analyze the changes in the number, activation level and cytokine secretion ability of MAIT cells in mouse adipose tissue after cold stimulation. In a co-culture system of MAIT cells and adipocytes, the effect of interleukin-4 (IL-4) blocking antibodies on the expressions of brown adipose tissue markers in the adipocytes was evaluated using Western blotting and RT-PCR. In a mouse model of MAIT cell deficiency, the changes in adipose browning-related indicators in response to cold stimulation were analyzed using metabolic cages, immunohistochemistry, Western blotting and the Seahorse method. Results In both the mouse models of functional deficiency of MAIT cells and wild-type mice, cold stimulation significantly increased the expression levels of brown adipose tissue markers UCP-1 and PGC1-α and upregulated CD69 and IL-4 expressions in the adipose tissue without significantly affecting the number of MAIT cells in the adipose tissue. In the co-culture experiment, the adipocytes showed obviously increased browning level after co-culture with MAIT cells (P<0.05), but blocking IL-4 signaling strongly downregulated the browning level (P<0.05). The MAIT cell-deficient mice showed obviously lower levels of energy expenditure, adipose browning and metabolism of the adipocytes compared with the wild-type mice in response to cold stimulation (P<0.05). Conclusion MAIT cells participate in adipose browning in mice, and cold stimulation promotes MAIT cell secretion of IL-4 to positively regulate adipose browning.

Key words: mucosal-associated invariant T cells; obesity; brown adipose tissue