Himmel Megan E, Hardenberg Gijs, Piccirillo Ciriaco A, Steiner Theodore S, Levings Megan K
Department of Surgery, University of British Columbia, and Immunity and Infection Research Centre, Vancouver Coastal Health Research Institute, Vancouver, Canada.
Immunology. 2008 Oct;125(2):145-53. doi: 10.1111/j.1365-2567.2008.02939.x.
Two related chronic inflammatory diseases, Crohn's disease and ulcerative colitis, are together often referred to as inflammatory bowel disease (IBD). Current treatment options are not curative, and patients face lifelong therapy and debilitation. IBD is thought to be the product of a combination of genetic and environmental factors that result in the abnormal regulation of immune responses. Experimental models have demonstrated that normal CD4+ T-regulatory (Treg) cell responses and commensal bacteria are required for the maintenance of gut immune homeostasis. Recent evidence that CD4+ T cells express Toll-like receptors (TLRs) and respond directly to TLR ligands, suggests that signals from commensal bacteria may directly affect T-cell responses in the gut. In this review, we focus on evidence that defects in Treg cells may underlie IBD in humans. In addition, we discuss evidence that direct signaling via TLRs to T cells can affect IBD and that T-cell-dependent responses to bacterial proteins, such as flagellin, are central to the aetiology of this disease.
两种相关的慢性炎症性疾病，克罗恩病和溃疡性结肠炎，通常合称为炎症性肠病（IBD）。目前的治疗方案无法治愈，患者面临终身治疗和身体衰弱。IBD被认为是遗传和环境因素共同作用的结果，这些因素导致免疫反应的异常调节。实验模型表明，正常的CD4 +调节性T（Treg）细胞反应和共生细菌是维持肠道免疫稳态所必需的。最近有证据表明，CD4 + T细胞表达Toll样受体（TLR）并直接对TLR配体作出反应，这表明来自共生细菌的信号可能直接影响肠道中的T细胞反应。在这篇综述中，我们重点关注Treg细胞缺陷可能是人类IBD基础的证据。此外，我们讨论了通过TLR直接向T细胞发出信号可影响IBD的证据，以及T细胞对细菌蛋白（如鞭毛蛋白）的依赖性反应是该疾病病因的核心。
