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

First Author  Zhang Z Year  2019
Journal  Mol Med Rep Volume  19
Issue  3 Pages  1840-1848
PubMed ID  30628695 Mgi Jnum  J:295140
Mgi Id  MGI:6459682 Doi  10.3892/mmr.2019.9823
Citation  Zhang Z, et al. (2019) Aryl hydrocarbon receptor activation modulates gammadelta intestinal intraepithelial lymphocytes and protects against ischemia/reperfusion injury in the murine small intestine. Mol Med Rep 19(3):1840-1848
abstractText  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 gammadelta (gammadelta) intraepithelial lymphocytes (IELs), is thought to regulate inflammation in the bowel. gammadeltaIELs are a key immunologic compartment with a capacity to modulate immune responses. In the present study, the function of the AhR in gammadeltaIELs 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+6formylindolo(3,2b)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 microg 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 gammadeltaIELs and activation of CD4+ and CD8+ IELs were examined using flow cytometry. The cytokine mRNA and antiapoptosis gene expression in IELs were measured by qPCR. FICZ increased the gammadeltaIEL population and antiapoptosis genes in the gammadeltaIELs. FICZ reduced the percentage of activated CD4+ and CD8+ subpopulations and the expression of proinflammatory 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 gammadeltaIEL population by decreasing apoptosis of gammadeltaIELs.
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