The Probable Role of Tregs in Improved Heat Tolerance in Heat-acclimated Mice

Abstract Heatstroke is a life-threatening illness related to systematic inflammation-induced multiple organ dysfunction. The severity of systematic inflammatory response may be related to the changes in immune regulation triggered by heat acclimation. However, the mechanisms of heat acclimation and its effect on immune regulation are unclear. Here, we assessed the differences in immunocyte subsets in the spleen and lymph nodes of heat-acclimated mice. Higher frequencies of CD4+ Foxp3+ regulatory T cells (Tregs) were observed in the heat-acclimated mice. Our results indicate that the improvement in heat tolerance during acute heat stress correlates with the increase in the number of Tregs. These Tregs mitigated the recruitment of neutrophils, inhibited their activation, and suppressed the severity of acute inflammation. The increased differentiation and development of Tregs might stem from an enhanced expression of Foxp3 and PD-L1. Our results strongly suggest that the increase of Tregs has a regulatory effect on neutrophils, and that the PD-1/PD-L1 pathway may be involved in this regulation. The anti-inflammatory effects of Tregs have never been studied in the context of heat stress-induced systemic inflammation. Thus, the results of our study are significant for devising a potential treatment for systemic inflammatory response syndrome and heatstroke. National Natural Science Foundation of China (grant number 81570497)