Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage.
Cutting Edge: IL-36 Receptor Promotes Resolution of Intestinal Damage.
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DOI：
10.4049/jimmunol.1501312
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发表时间：
2016-01-01
期刊：
影响因子：
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通讯作者：
Denning TL
中科院分区：
文献类型：
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作者：
Medina-Contreras O;Harusato A;Nishio H;Flannigan KL;Ngo V;Leoni G;Neumann PA;Geem D;Lili LN;Ramadas RA;Chassaing B;Gewirtz AT;Kohlmeier JE;Parkos CA;Towne JE;Nusrat A;Denning TL
白细胞介素-1家族成员是宿主防御的中心介质。在这里，我们发现新的IL-1家族成员IL-36γ在实验性结肠炎和人类炎症性肠病（IBD）中表达。在葡聚糖硫酸钠（DSS）诱导的损伤中，无菌（GF）小鼠无法诱导IL-36γ，这表明肠道微生物群参与了其诱导。令人惊讶的是，il - 36r缺陷（Il1rl2−/−）小鼠在dss诱导的损伤和结肠粘膜活检伤口闭合受损后表现出恢复缺陷，这与伤口床中性粒细胞积累受损相一致。Il1rl2−/−小鼠从dss诱导的损伤中恢复失败与IL-22表达的显著降低有关，特别是结肠中性粒细胞的表达。用芳烃受体（AhR）激动剂可以挽救Il1rl2−/−小鼠的缺陷恢复，这足以恢复IL-22的表达，促进dss诱导的损伤的完全恢复。这些发现提示IL-36/IL-36R轴参与肠黏膜损伤的消退。
Interleukin-1 family members are central mediators of host defense. Here we show that the novel IL-1 family member, IL-36γ, was expressed during experimental colitis and human inflammatory bowel disease (IBD). In response to dextran sodium sulfate (DSS)-induced damage, germ-free (GF) mice failed to induce IL-36γ, suggesting that gut microbiota are involved in its induction. Surprisingly, IL-36R-deficient (Il1rl2−/−) mice exhibited defective recovery following DSS-induced damage and impaired closure of colonic mucosal biopsy wounds, which coincided with impaired neutrophil accumulation in the wound bed. Failure of Il1rl2−/− mice to recover from DSS-induced damage was associated with a profound reduction in IL-22 expression, particularly by colonic neutrophils. Defective recovery of Il1rl2−/− mice could be rescued an aryl hydrocarbon receptor (AhR) agonist, which was sufficient to restore IL-22 expression and promote full recovery from DSS-induced damage. These findings implicate the IL-36/IL-36R axis in the resolution of intestinal mucosal wounds.