6-Formylindolo (3, 2-b) Carbazole (FICZ) is a ligand of aryl hydrocarbon receptor (AHR) which regulates Th17 release of IL-17 and IL-22 production. Earlier, we showed that ethanol combined with burn injury suppresses Th17 responses and disrupts intestinal barrier leading to increased gut bacterial growth and translocation. Since IL-22 is known for its role in intestinal barrier maintenance, we determined whether treatment of mice with FICZ restores T cell IL-22 release and protects intestine barrier following ethanol and burn injury. Wildtype and Rag1−/− mice were gavaged with ~2.9 g/kg ethanol or water, and given a ~12.5% total body surface area burn. Mice were given FICZ (5 μg) in resuscitation fluid. FICZ treatment of wildtype mice normalized IL-22 and IL-17 in lamina propria and spleen T cells, as well as increased CYP1A1 expression in spleen T cells. This was accompanied by improved gut motility, decreased copy number of small intestine total bacteria and Enterobacteriaceae, attenuation of intestinal tissue levels of IL-6, KC, IL-18, decreased apoptosis, and prevention of gut leakiness following ethanol and burn injury. However, FICZ treatment of Rag1−/− mice did not improve any of the parameters listed after ethanol and burn injury. Additional data generated using mice treated with recombinant IL-22 alone or in combination with anti-IL-18 antibody suggest that full protection of gut barrier integrity requires both IL-18 inhibition and IL-22 restoration following ethanol and burn injury. Together our findings suggest that AHR ligand FICZ may have better therapeutic potential for maintenance of gut barrier function after ethanol and burn injury.

6-Formylindolo (3, 2-b) Carbazole (FICZ) 是芳烃受体 (AHR) 的配体，可调节 IL-17 的 Th17 释放和 IL-22 的产生。早些时候，我们表明乙醇与烧伤相结合会抑制 Th17 反应并破坏肠道屏障，导致肠道细菌生长和易位增​​加。由于 IL-22 以其在肠道屏障维持中的作用而闻名，我们确定了用 FICZ 治疗小鼠是否能恢复 T 细胞 IL-22 释放并在乙醇和烧伤后保护肠道屏障。野生型和 Rag1-/- 小鼠被灌胃约 2.9 g/kg 乙醇或水，并给予约 12.5% 的总体表面积烧伤。给予小鼠复苏液中的 FICZ (5 μg)。FICZ 对野生型小鼠的处理使固有层和脾脏 T 细胞中的 IL-22 和 IL-17 正常化，以及脾T细胞中CYP1A1表达增加。这伴随着肠道运动的改善，小肠总细菌和肠杆菌科的拷贝数减少，IL-6、KC、IL-18 的肠组织水平降低，细胞凋亡减少，以及乙醇和烧伤后肠道渗漏的预防。然而，FICZ 对 Rag1-/- 小鼠的治疗并未改善乙醇和烧伤后列出的任何参数。使用重组 IL-22 单独治疗或与抗 IL-18 抗体联合治疗的小鼠产生的其他数据表明，肠道屏障完整性的完全保护需要 IL-18 抑制和乙醇和烧伤后 IL-22 恢复。