PT  - JOURNAL ARTICLE
AU  - Minyue Qiu
AU  - Yuxin Zhou
AU  - Nan Ye
AU  - Hongxia Guo
AU  - Xiaoyang Zhou
AU  - Xiaoyan Ding
AU  - Jintao Li
TI  - Improved Heat Tolerance in Heat-acclimated Mice: The Probable Role of the PD-L1 Pathway
AID  - 10.1101/2022.02.20.481185
DP  - 2022 Jan 01
TA  - bioRxiv
PG  - 2022.02.20.481185
4099  - http://biorxiv.org/content/early/2022/02/20/2022.02.20.481185.short
4100  - http://biorxiv.org/content/early/2022/02/20/2022.02.20.481185.full
AB  - Heat stroke is a life-threatening illness and is related to systematic inflammation-induced multiple organ dysfunction. Available evidence indicates that the severity of the systematic inflammatory response in heat stroke may be related to the changes in immune regulation brought by heat acclimation. However, the mechanisms of heat acclimation are still unclear. Here, we assessed the differences in immunocyte subsets in the spleen and lymph nodes of heat-acclimated and unacclimated mice. A higher frequency of CD4+Foxp3+ Tregs was observed in heat-acclimated mice. Our results indicated that the improved heat tolerance exhibited during acute heat stress exposure was related to an increased number of Tregs. In heat-acclimated mice, an increase in the number of Tregs was able to mitigate the recruitment of neutrophils, inhibit the activation of neutrophils, and suppress the severity of acute inflammation. Increased differentiation and development of Tregs in peripheral immune organs in heat-acclimated mice might stem from enhanced expression of Foxp3 and PD-L1. Our results strongly suggest that the regulatory function of increased Tregs on neutrophils may be regulated through the PD-1/PD-L1 pathway. The anti-inflammatory effects of Tregs have never been studied in the context of heat stress-induced systemic inflammation. Thus, our results on immunoregulation involving Tregs in heat-acclimated mice might be significant for devising a potential treatment for systemic inflammatory response syndrome and heatstroke.Competing Interest StatementThe authors have declared no competing interest.