Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses.
Dietary and Microbial Oxazoles Induce Intestinal Inflammation by Modulating Aryl Hydrocarbon Receptor Responses.
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DOI：
10.1016/j.cell.2018.04.037
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发表时间：
2018-05-17
期刊：
影响因子：
64.5
通讯作者：
Blumberg RS
中科院分区：
文献类型：
--
作者：
Iyer SS;Gensollen T;Gandhi A;Oh SF;Neves JF;Collin F;Lavin R;Serra C;Glickman J;de Silva PSA;Sartor RB;Besra G;Hauser R;Maxwell A;Llebaria A;Blumberg RS
全基因组关联研究已经确定了与炎症性肠病发生相关的风险位点，而流行病学研究强调，发病机制可能涉及宿主与环境元素的相互作用，其来源和结构需要确定。在这里，我们鉴定了一类源自饮食、微生物和工业来源的化合物，其特征是存在五元恶唑环并诱导 CD1d 依赖性肠道炎症。我们观察到最小恶唑结构通过调节肠上皮细胞 (IEC) 上 CD1d 的脂质抗原呈递来调节自然杀伤 T 细胞依赖性炎症。 IEC 产生的 CD1d 限制的白细胞介素 10 受到芳烃受体 (AhR) 途径响应色氨酸代谢物恶唑诱导的活性的限制。因此，肠上皮细胞中 AhR 的消耗消除了恶唑诱导的炎症。总之，我们确定环境来源的恶唑是 CD1d 依赖性肠道炎症反应的触发因素，这种炎症反应是通过激活肠上皮中的 AhR 而发生的。一类微生物和环境化合物通过自然杀伤 T 细胞和芳烃受体信号传导的作用引发肠道上皮细胞炎症。
Genome-wide association studies have identified risk loci associated with the development of inflammatory bowel disease, while epidemiological studies have emphasized that pathogenesis likely involves host interactions with environmental elements whose source and structure need to be defined. Here, we identify a class of compounds derived from dietary, microbial, and industrial sources that are characterized by the presence of a five-membered oxazole ring and induce CD1d-dependent intestinal inflammation. We observe that minimal oxazole structures modulate natural killer T cell-dependent inflammation by regulating lipid antigen presentation by CD1d on intestinal epithelial cells (IECs). CD1d-restricted production of interleukin 10 by IECs is limited through activity of the aryl hydrocarbon receptor (AhR) pathway in response to oxazole induction of tryptophan metabolites. As such, the depletion of the AhR in the intestinal epithelium abrogates oxazole-induced inflammation. In summary, we identify environmentally derived oxazoles as triggers of CD1d-dependent intestinal inflammatory responses that occur via activation of the AhR in the intestinal epithelium. A class of microbial and environmental compounds triggers inflammation in gut epithelial cells through the action of natural killer T cells and aryl hydrocarbon receptor signaling.
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DOI：
10.1126/science.1219328
发表时间：
2012-04-27
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Olszak T;An D;Zeissig S;Vera MP;Richter J;Franke A;Glickman JN;Siebert R;Baron RM;Kasper DL;Blumberg RS
通讯作者：
Blumberg RS
由替代启动子调节的MTP对于NKT细胞发育至关重要。
DOI：
10.1084/jem.20062006
发表时间：
2007-03-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
通讯作者：
--
影响因子：
64.8
作者：
Olszak, Torsten;Neves, Joana F.;Dowds, C. Marie;Baker, Kristi;Glickman, Jonathan;Davidson, Nicholas O.;Lin, Chyuan-Sheng;Jobin, Christian;Brand, Stephan;Sotlar, Karl;Wada, Koichiro;Katayama, Kazufumi;Nakajima, Atsushi;Mizuguchi, Hiroyuki;Kawasaki, Kunito;Nagata, Kazuhiro;Mueller, Werner;Snapper, Scott B.;Schreiber, Stefan;Kaser, Arthur;Zeissig, Sebastian;Blumberg, Richard S.
通讯作者：
Blumberg, Richard S.
影响因子：
29.7
作者：
Kaser A;Zeissig S;Blumberg RS
通讯作者：
Blumberg RS
DOI：
10.1084/jem.20030437
发表时间：
2004-02-16
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Iijima H;Neurath MF;Nagaishi T;Glickman JN;Nieuwenhuis EE;Nakajima A;Chen D;Fuss IJ;Utku N;Lewicki DN;Becker C;Gallagher TM;Holmes KV;Blumberg RS
通讯作者：
Blumberg RS