Regulatory T Cells Could Improve Intestinal Barrier Dysfunction in Heatstroke
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ORIGINAL ARTICLE
Regulatory T Cells Could Improve Intestinal Barrier Dysfunction in Heatstroke Jie Hu,1 Hongjun Kang,1 Chao Liu,1 Pan Hu,1 Mengmeng Yang,1 and Feihu Zhou1,2
Intestinal barrier dysfunction plays a pivotal role in multiorgan dysfunction during heatstroke (HS). Neutrophils are involved in intestinal inflammation and thus dampen the mucosal integrity. Regulatory T cells (Tregs) have been shown to orchestrate neutrophils and thus sustain mucosal integrity in miscellaneous inflammation-related diseases. However, whether Tregs are involved in HS-induced intestinal barrier dysfunction remains unknown. Thus, we investigated whether Tregs could alleviate intestinal barrier dysfunction in mice. We found that HS could induce intestinal injury and mucosal barrier dysfunction 0, 24, and 72 h after heat stress. Flow cytometry revealed an increase of neutrophil infiltration and a decrease of Treg frequencies in the small intestinal epithelium 72 h after heat stress. Treg depletion starting 2 days before HS exacerbated intestinal damage and mucosal barrier dysfunction. Adoptive transfer of Tregs at 0 h improved intestinal injury and mucosal barrier dysfunction at 72 h. The manipulation of Tregs affected the neutrophil frequencies in the small intestinal epithelium 72 h after heat stress. Our study demonstrated that Tregs could improve HSinduced intestinal barrier dysfunction, probably via modulation of neutrophils in the intestine of mice during HS.
Abstract—
KEY WORDS: heatstroke; regulatory T cells; neutrophils; intestinal barrier dysfunction.
INTRODUCTION Heatstroke (HS) is a life-threatening injury that is characterized by central nervous system dysfunction and hyperthermia (core temperature > 40 °C). Despite rapid cooling and organ support therapy, many patients still quickly progress to multiple organ dysfunction syndromes (MODS) and experience permanent neurological impairments or death [24].
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10753-019-00983-6) contains supplementary material, which is available to authorized users. 1
Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China 2 To whom correspondence should be addressed at Critical Care Medicine, Chinese PLA General Hospital, 28th Fuxing Road, Haidian District, Beijing, 100853, China. E-mail: [email protected]
Gut-derived endotoxin caused by intestinal barrier dysfunction has been considered as the Bmotor^ of MODS in critically ill patients [17]. Emerging evidence has shown that the intestine is highly susceptible to heat injury [21, 30] and gut-derived endotoxin plays a pivotal role in the development of systemic inflammatory response syndrome (SIRS) and MODS in HS patients [12, 18, 26]. The pro-inflammatory cytokines in the intestine are associated with intestinal injury during HS [27]. Neutrophils are involved in intestinal inflammation and mucosal integrity [33]. Meanwhile, inflammatory conditions in the intestinal mucosa further c
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