Aryl hydrocarbon receptor activation modulates γδ intestinal intraepithelial lymphocytes and protects against ischemia/reperfusion injury in the murine small intestine

Zhang,Zhicao; Pu,Aimin; Yu,Min; Xiao,Weidong; Sun,Lihua; Cai,Yujiao; Yang,Hua

doi:10.3892/mmr.2019.9823

Aryl hydrocarbon receptor activation modulates γδ intestinal intraepithelial lymphocytes and protects against ischemia/reperfusion injury in the murine small intestine

Authors:
- Zhicao Zhang
- Aimin Pu
- Min Yu
- Weidong Xiao
- Lihua Sun
- Yujiao Cai
- Hua Yang
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Affiliations: Department of General Surgery, Xinqiao Hospital, Army Medical University, Chongqing 400037, P.R. China
Published online on: January 4, 2019 https://doi.org/10.3892/mmr.2019.9823
Pages: 1840-1848

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Abstract

The pathogenesis of intestinal ischemia/reperfusion (I/R) is associated with dysregulation of the intestinal immune system. The aryl hydrocarbon receptor (AhR), a receptor expressed in gamma‑delta (γδ) intraepithelial lymphocytes (IELs), is thought to regulate inflammation in the bowel. γδIELs are a key immunologic compartment with a capacity to modulate immune responses. In the present study, the function of the AhR in γδIELs in a mouse model of intestinal I/R injury was investigated to determine whether the AhR attenuates intestinal injury induced by intestinal I/R. Mice were assigned to three groups: sham, I/R and I/R+6‑formylindolo(3,2‑b)carbazole (FICZ). The sham group received no ischemia treatment, whereas the I/R and I/R+FICZ groups underwent upper mesenteric vessel ischemia for 30 min. The I/R group was injected intraperitoneally with 0.3 ml saline and the I/R+FICZ group was administered 1 µg of FICZ before a subsequent 6 h reperfusion. Then, the mice were sacrificed and the entire small intestinal tissues were collected for histologic examination. The phenotype and apoptosis of γδIELs and activation of CD4+ and CD8+ IELs were examined using flow cytometry. The cytokine mRNA and anti‑apoptosis gene expression in IELs were measured by qPCR. FICZ increased the γδIEL population and anti‑apoptosis genes in the γδIELs. FICZ reduced the percentage of activated CD4+ and CD8+ subpopulations and the expression of pro‑inflammatory mediator genes in IELs. FICZ inhibited inflammation in the gastrointestinal tract of mice with I/R injury. These results suggest that the AhR plays an important role in protecting the small intestine from I/R and increasing the γδIEL population by decreasing apoptosis of γδIELs.

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