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  2. Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis

Glutamine alleviates intestinal injury in a murine burn sepsis model by maintaining intestinal intraepithelial lymphocyte homeostasis

  • Eur J Pharmacol. 2022 Dec 21;940:175480. doi: 10.1016/j.ejphar.2022.175480.
Xiaoli Chen 1 Yuanfeng Zhu 1 Yan Wei 1 Shijun Fan 1 Lin Xia 1 Qian Chen 1 Yongling Lu 1 Dan Wu 1 Xin Liu 2 Xi Peng 3
Affiliations

Affiliations

  • 1 Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China.
  • 2 Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: liux0704@tmmu.edu.cn.
  • 3 Clinical Medical Research Center, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China; State Key Laboratory of Trauma, Burns and Combined Injury, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: pxlrmm@tmmu.edu.cn.
Abstract

Intestinal intraepithelial lymphocytes (IELs) play a sentinel role in the mucosal immune system because of their unique anatomical location in the epithelial layer. The disruption of IEL homeostasis is implicated in driving the intestinal injury of many typical inflammatory disorders, such as inflammatory bowel disease (IBD) and sepsis. Therefore, it is meaningful to alleviate intestinal injury by restoring IEL homeostasis in disease conditions. This study explores the effects of glutamine on intestinal IEL homeostasis in a murine model of burn sepsis. We report that glutamine inhibits inflammatory response and reduces injury in the small intestine of burn septic mice. This effect is attributed to the maintaining of IEL homeostasis by suppressing Apoptosis and restoring the disrupted subpopulation balance induced by burn sepsis. Mechanistically, we show that glutamine does not affect the IL-15 dependent mechanisms that drive the maintenance and differentiation of IELs. Instead, glutamine sustains IEL homeostasis by upregulate Aryl Hydrocarbon Receptor (AHR) and interleukin (IL)-22 transcription and expression. Consistently, the protective roles of glutamine in burn septic mice were repressed by further supplement with an AHR antagonist CH-223191. Collectively, our study reveals a new role of glutamine to maintain IEL homeostasis by activating the AHR signaling pathway, which in turn ameliorates intestinal injury in burn sepsis.

Keywords

AHR; Burn sepsis; Glutamine; IEL homeostasis; IELs.

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