Epigenetic regulation of epithelial dectin-1 through an IL-33-STAT3 axis in allergic disease.
Epigenetic regulation of epithelial dectin-1 through an IL-33-STAT3 axis in allergic disease.
复制标题
作者：
过敏性疾病在易感人群中出现，部分原因是保护途径的减少。这些抗炎分子被抑制的机制尚不清楚。我们之前已经报道过，上皮Dectin-1可以防止异常的2型反应，并且在过敏患者的上皮细胞中下调。在此，我们报道了人类呼吸道上皮细胞结构性地表达Dectin-1，并且IL-33特异性地作为Dectin-1的抑制因子。从机制上讲，这是通过依赖IL-33的STAT3激活和随后抑制Dectin-1基因CLEC7A来实现的。我们已经确定了CLEC7A近端启动子上游的一个新的增强子区域，该区域仅在上皮细胞中可访问，而在造血细胞中不能。通过这个新发现的位于IL-33-STAT3轴下游的新发现的基因位点，CLEC7A的表观遗传学抑制发生在过敏个体的上皮细胞中。总而言之，我们的数据确定了一种可能参与过敏反应的上皮细胞中Dectin-1表达的表观遗传微调机制。
Allergic diseases arise in susceptible individuals in part because of decrements in protective pathways. The mechanism by which these anti-inflammatory molecules become repressed remains unclear. We have previously reported that epithelial dectin-1 prevents aberrant type 2 responses and is downregulated in the epithelium of allergic patients. Here we report that dectin-1 is constitutively expressed by the respiratory epithelium in humans, and that IL-33 specifically acts as a repressor of dectin-1. Mechanistically, this occurs via IL-33-dependent STAT3 activation and the subsequent repression of the dectin-1 gene, CLEC7A. We have identified a novel enhancer region upstream of the proximal promoter of CLEC7A that is only accessible in epithelial cells, but not in hematopoietic cells. Epigenetic repression of CLEC7A through this newly identified locus, downstream of an aberrant IL-33-STAT3 axis, occurs in the epithelium of allergic individuals. Collectively, our data identify a mechanism of epigenetic fine-tuning of dectin-1 expression in epithelial cells that may participate in allergenicity.
登录
查看更多内容
影响因子：
14.2
作者：
Reese, Sarah E.;Xu, Cheng-Jian;London, Stephanie J.
通讯作者：
London, Stephanie J.
影响因子：
--
作者：
Ramadoss, Preeti;Unger-Smith, Nathan E.;Hollenberg, Anthony N.
通讯作者：
Hollenberg, Anthony N.
Dectin-1在人肺中表达，并介导对不可能的流感嗜血杆菌的促炎性免疫反应。
影响因子：
6.4
作者：
Heyl KA;Klassert TE;Heinrich A;Müller MM;Klaile E;Dienemann H;Grünewald C;Bals R;Singer BB;Slevogt H
通讯作者：
Slevogt H
影响因子：
5.8
作者：
Holik, Aliaksei Z.;Filby, Caitlin E.;Asselin-Labat, Marie-Liesse
通讯作者：
Asselin-Labat, Marie-Liesse
影响因子：
8
作者：
Kim, J. Y.;Lim, S-C;Choi, H. S.
通讯作者：
Choi, H. S.