LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium.
LRRC31 is induced by IL-13 and regulates kallikrein expression and barrier function in the esophageal epithelium.
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DOI：
10.1038/mi.2015.98
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发表时间：
2016-05
影响因子：
8
通讯作者：
Rothenberg ME
中科院分区：
文献类型：
--
作者：
D'Mello RJ;Caldwell JM;Azouz NP;Wen T;Sherrill JD;Hogan SP;Rothenberg ME
嗜酸性食管炎(EoE)是一种以食道白介素13(IL-13)水平升高和屏障功能受损为特征的过敏性食管炎性疾病。在此，我们研究了富含亮氨酸重复序列的蛋白31(LRRC31)在人EoE食道组织和IL-13处理的食道上皮细胞中的表达。LRRC31在结肠和呼吸道粘膜上皮细胞中均有基础mRNA表达。活动期EoE患者食道LRRC31mRNA和蛋白表达增加，并与食管嗜酸性粒细胞增多症、IL13和CCL26mRNA表达密切相关。IL-13作用于气液界面分化的食道上皮细胞(EPC2s)，LRRC31mRNA和蛋白表达增加。在基线时，分化的LRRC31过表达EPC2细胞的屏障功能增强(跨上皮电阻增加1.9倍[P<；0.05]，细胞旁流量减少2.8倍[P<；0.05])。对分化的LRRC31过表达的EPC2进行RNA测序分析，发现38个异常基因(P<；0.05)，包括5个激肽释放酶(KLK)丝氨酸蛋白酶。值得注意的是，分化的LRRC31过表达的EPC2细胞降低了KLK的表达和活性，而IL-13处理的分化的LRRC31基因沉默的EPC2细胞增加了KLK的表达和基底上皮脱离。我们在活动期EoE患者和IL-13处理的食道上皮细胞中发现了类似的KLK异常表达。我们认为LRRC31是由IL-13诱导的，并可能通过KLK调节上皮屏障功能。
Eosinophilic esophagitis (EoE) is an allergic inflammatory disease of the esophagus featuring increased esophageal interleukin 13 (IL-13) levels and impaired barrier function. Herein, we investigated leucine-rich repeat–containing protein 31 (LRRC31) in human EoE esophageal tissue and IL-13–treated esophageal epithelial cells. LRRC31 had basal mRNA expression in colonic and airway mucosal epithelium. Esophageal LRRC31 mRNA and protein increased in active EoE and strongly correlated with esophageal eosinophilia and IL13 and CCL26 mRNA expression. IL-13 treatment increased LRRC31 mRNA and protein in air-liquid interface–differentiated esophageal epithelial cells (EPC2s). At baseline, differentiated LRRC31-overexpressing EPC2s had increased barrier function (1.9-fold increase in transepithelial electrical resistance [P < 0.05] and 2.8-fold decrease in paracellular flux [P < 0.05]). RNA sequencing analysis of differentiated LRRC31-overexpressing EPC2s identified 38 dysregulated genes (P < 0.05), including 5 kallikrein (KLK) serine proteases. Notably, differentiated LRRC31-overexpressing EPC2s had decreased KLK expression and activity, whereas IL-13–treated, differentiated LRRC31 gene-silenced EPC2s had increased KLK expression and suprabasal epithelial detachment. We identified similarly dysregulated KLK expression in the esophagus of patients with active EoE and in IL-13–treated esophageal epithelial cells. We propose that LRRC31 is induced by IL-13 and modulates epithelial barrier function, potentially through KLK regulation.