A dendritic cell population responsible for transglutaminase 2-mediated gluten antigen presentation in celiac disease.

ABSTRACT: In celiac disease (CeD), a gluten-dependent autoimmune disorder, transglutaminase 2 (TG2), deamidates selected glutamine residues in gluten peptides, while HLA-DQ2 presents deamidated antigens to inflammatory T cells. The cellular sources of pathogenic TG2 and DQ2 are unclear. Using chemical biology tools, we show that intestinal CD103+ dendritic cells (DCs) couple cell-surface TG2 to the endocytic LRP1 receptor to simultaneously deamidate gluten antigens and concentrate them in lysosomes. In DQ2-transgenic mice, CD103+ DCs loaded with deamidated antigens migrate from intestinal lamina propria and Peyer's patches into mesenteric lymph nodes, where they engage T cells. In turn, gluten antigen presentation upregulates intestinal TG2 activity. The tool (HB-230) used to establish a role of CD1

SUBMITTER: Yang FC 

PROVIDER: S-EPMC12513477 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature