Pathogenic and protective roles of MyD88 in leukocytes and epithelial cells in mouse models of inflammatory bowel disease.
Pathogenic and protective roles of MyD88 in leukocytes and epithelial cells in mouse models of inflammatory bowel disease.
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DOI：
10.1053/j.gastro.2010.04.045
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发表时间：
2010-08
期刊：
影响因子：
29.4
通讯作者：
Maloy KJ
中科院分区：
文献类型：
--
作者：
Asquith MJ;Boulard O;Powrie F;Maloy KJ
Toll样受体（TLR）是参与识别肠道微生物菌群的先天性免疫受体;它们由肠道中的多种细胞类型表达，包括上皮细胞、骨髓细胞和淋巴细胞。关于TLR信号在不同细胞区室中对肠内稳态的相对贡献知之甚少。我们的目的是确定TLR信号在不同类型的细胞中在慢性肠道炎症的诱导和调节中的作用。我们评估了共享的TLR信号转导衔接蛋白MyD 88在几种互补的炎症性肠病（IBD）小鼠模型中的作用，这些炎症性肠病由先天性或适应性免疫激活介导。MyD 88缺陷小鼠和骨髓嵌合体用于选择性地破坏肠中不同细胞区室中的TLR信号。骨髓细胞的MyD 88依赖性活化是慢性肠道炎症发展所必需的。相比之下，虽然上皮细胞MyD 88信号是宿主生存所必需的，但在缺乏MyD 88感受态髓样区室的情况下，它们不足以诱导肠道炎症。T细胞表达MyD 88并不是其在肠道中的致病和调节功能所必需的。肠中MyD 88信号的细胞区室化允许维持宿主防御并防止有害的炎症反应。
Toll-Like Receptors (TLR) are innate immune receptors involved in recognition of the intestinal micro-flora; they are expressed by numerous cell types in the intestine, including epithelial cells, myeloid cells and lymphocytes. Little is known about the relative contributions of TLR signaling in distinct cellular compartments to intestinal homeostasis. We aimed to define the roles of TLR signals in distinct cell types in the induction and regulation of chronic intestinal inflammation. We assessed the roles of the shared TLR signaling adaptor protein, MyD88, in several complementary mouse models of inflammatory bowel disease (IBD), mediated by either innate or adaptive immune activation. MyD88-deficient mice and bone marrow chimeras were used to selectively disrupt TLR signals in distinct cellular compartments in the intestine. MyD88-dependent activation of myeloid cells was required for development of chronic intestinal inflammation. By contrast, although epithelial cell MyD88 signals were required for host survival, they were insufficient to induce intestinal inflammation in the absence of a MyD88-competent myeloid compartment. MyD88 expression by T cells was not required for their pathogenic and regulatory functions in the intestine. Cellular compartmentalization of MyD88 signals in the intestine allow the maintenance of host defense and prevent deleterious inflammatory responses.
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影响因子：
32.4
作者：
Hou, Baidong;Reizis, Boris;DeFranco, Anthony L.
通讯作者：
DeFranco, Anthony L.
影响因子：
56.9
作者：
Peng, GY;Guo, Z;Wang, RF
通讯作者：
Wang, RF
DOI：
10.1073/pnas.2534546100
发表时间：
2003-12-23
影响因子：
11.1
作者：
Kullberg, MC;Andersen, JF;Sher, A
通讯作者：
Sher, A
影响因子：
3.2
作者：
Michelsen, Kathrin S.;Arditi, Moshe
通讯作者：
Arditi, Moshe
影响因子：
4.4
作者：
Karrasch, Thomas;Kim, Joo-Sung;Jobin, Christian
通讯作者：
Jobin, Christian