Role of gut epithelial-cell derived transglutaminase 2 in the formation of celiac disease autoantibodies
Formation of autoantibodies to transglutaminase 2 (TG2) in celiac disease likely involves TG2-gluten complexes that allow gluten-specific CD4+ T cells to provide help to TG2-specific B cells. To investigate whether TG2 derived from intestinal epithelial cells (IECs) contributes to this process, we generated mice with inducible IEC-specific expression of TG2 fused to a deamidated gluten peptide…
A recent study has shed light on the potential role of gut epithelial-cell derived transglutaminase 2 (TG2) in the development of celiac disease autoantibodies. The research indicates that TG2-gluten complexes may facilitate the interaction between gluten-specific CD4+ T cells and TG2-specific B cells, thereby contributing to the autoimmune response.
To explore this hypothesis, scientists generated mice with the ability to produce TG2 fused to a deamidated gluten peptide (DGP) containing a T-cell epitope. When this TG2-DGP fusion protein was expressed in intestinal epithelial cells (IECs) and released into the intestinal lumen, it proved immunogenic in mice with activated gluten-specific CD4+ T cells and naive TG2-specific B cells.
The resulting production of intestinal and systemic anti-TG2 autoantibodies supports the idea that TG2, when derived from intestinal epithelial cells, plays a pathogenic role in driving anti-TG2 autoimmunity in celiac disease.
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