Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.
Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Department of Chemical Engineering, Stanford University, Stanford, CA 94305, USA; Sarafan ChEM-H (Chemistry, Engineering and Medicine for Human Health), Stanford University, Stanford, CA 94305, USA.
Trends Pharmacol Sci. 2023 Dec;44(12):949-962. doi: 10.1016/j.tips.2023.09.006. Epub 2023 Oct 14.
Celiac disease (CeD) is a widespread, gluten-induced, autoimmune disorder that lacks any medicinal therapy. Towards the goal of developing non-dietary treatments for CeD, research has focused on elucidating its molecular and cellular etiology. A model of pathogenesis has emerged centered on interactions between three molecular families: specific class II MHC proteins on antigen-presenting cells (APCs), deamidated gluten-derived peptides, and T cell receptors (TCRs) on inflammatory CD4 T cells. Growing evidence suggests that this pathogenic axis can be pharmacologically targeted to protect patients from some of the adverse effects of dietary gluten. Further studies have revealed the existence of additional host and environmental contributors to disease initiation and tissue damage. This review summarizes our current understanding of CeD pathogenesis and how it is being harnessed for therapeutic design and development.
乳糜泻（CeD）是一种广泛存在的、由麸质引起的自身免疫性疾病，目前尚无有效的治疗方法。为了开发非饮食治疗乳糜泻的方法，研究人员致力于阐明其分子和细胞病因。目前已经提出了一种发病机制模型，该模型围绕着三种分子家族之间的相互作用展开：抗原呈递细胞（APCs）上的特定 II 类 MHC 蛋白、脱酰胺麸质衍生肽和炎症性 CD4 T 细胞上的 T 细胞受体（TCR）。越来越多的证据表明，这条致病轴可以通过药物干预来保护患者免受饮食麸质的一些不良影响。进一步的研究揭示了宿主和环境因素在疾病起始和组织损伤中的额外作用。本文综述了我们目前对乳糜泻发病机制的理解，以及如何利用这些知识进行治疗设计和开发。
