Trends Pharmacol Sci. 2023 Dec;44(12):949-962. doi: 10.1016/j.tips.2023.09.006.Epub 2023 Oct 14.

Harrison A Besser ¹, Chaitan Khosla ²

Author information

¹Department of Chemistry, Stanford University, Stanford, CA 94305, USA; Stanford Medical Scientist Training Program, Stanford University School of Medicine, Stanford, CA 94305, USA.

²Department 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. Electronic address: khosla@stanford.edu.

Abstract

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.