生物
炎症
牙周炎
免疫学
疾病
自身免疫
上皮
微生物群
免疫系统
病理
医学
生物信息学
遗传学
内科学
作者
Tae Sung Kim,Tomoko Ikeuchi,Vasileios Ionas Theofilou,D. Williams,Teresa Greenwell-Wild,Armond June,Emmanuel E. Adade,Lu Li,Loreto Abusleme,Nicolás Dutzan,Yuan Yao,Laurie Brenchley,Nicolas Bouladoux,Yosuke Sakamachi,Robert Palmer,Ramiro Iglesias-Bartolomé,Giorgio Trinchieri,Stavros Garantziotis,Yasmine Belkaid,Alex M. Valm,Patricia I. Diaz,Steven M. Holland,Niki M. Moutsopoulos
出处
期刊:Immunity
[Elsevier]
日期:2024-04-01
卷期号:57 (4): 859-875.e11
被引量:1
标识
DOI:10.1016/j.immuni.2024.02.020
摘要
At mucosal surfaces, epithelial cells provide a structural barrier and an immune defense system. However, dysregulated epithelial responses can contribute to disease states. Here, we demonstrated that epithelial cell-intrinsic production of interleukin-23 (IL-23) triggers an inflammatory loop in the prevalent oral disease periodontitis. Epithelial IL-23 expression localized to areas proximal to the disease-associated microbiome and was evident in experimental models and patients with common and genetic forms of disease. Mechanistically, flagellated microbial species of the periodontitis microbiome triggered epithelial IL-23 induction in a TLR5 receptor-dependent manner. Therefore, unlike other Th17-driven diseases, non-hematopoietic-cell-derived IL-23 served as an initiator of pathogenic inflammation in periodontitis. Beyond periodontitis, analysis of publicly available datasets revealed the expression of epithelial IL-23 in settings of infection, malignancy, and autoimmunity, suggesting a broader role for epithelial-intrinsic IL-23 in human disease. Collectively, this work highlights an important role for the barrier epithelium in the induction of IL-23-mediated inflammation.
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