Coeliac disease organoids uncover key role of IL-7
2024
Stanford University School of Medicine, Stanford, USA
In this study, a human autoimmune organoid model was developed to investigate the gluten-dependent pathology of coeliac disease (CeD). Endoscopic biopsies from CeD patients were used to generate air-liquid interface duodenal organoids, preserving both the epithelium and the native mesenchyme, along with tissue-resident immune cells. Cell composition and immune responses to gluten peptides were analysed through histological analysis, immunomodulation, and single-cell RNA sequencing. The organoids contained diverse immune populations, including T, B, plasma, natural killer (NK), and myeloid cells, along with extensive T and B cell receptor repertoires. In CeD, gluten peptides trigger immune-mediated tissue damage by binding to the major histocompatibility complex (MHC) class II human leukocyte antigen molecules (HLA)-DQ2 or HLA-DQ8. Similarly, HLA-DQ2.5-expressing CeD organoids selectively exhibited epithelial damage when exposed to gluten peptides, and demonstrated gluten-induced immune responses. IL-7 was identified as a novel gluten-induced modulator, playing a key role in the activation of CD8+ T cells and epithelial destruction. Elevated IL-7 levels were also observed in biopsies from CeD patients during active disease compared to remission after a gluten-free diet.
A human autoimmune organoid model reveals IL-7 function in coeliac disease
Calvin J. Kuo
Added on: 03-24-2025
[1] https://www.nature.com/articles/s41586-024-07716-2
