Role of gut epithelial-cell derived transglutaminase 2 in the formation of celiac disease autoantibodies
- 1Oslo University Hospital
Abstract
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 (DGP) containing a T-cell epitope. Upon induction, the TG2-DGP fusion protein was expressed in IECs and released into the intestinal lumen. In HLA-DQ2.5 transgenic mice with activated gluten-specific CD4+ T cells and naive TG2-specific B cells, expression of TG2-DGP was immunogenic and drove the production of intestinal and systemic anti-TG2 autoantibodies. TG2-specific B cells predominantly expanded in Peyers patches, suggesting that their priming and subsequent differentiation into lamina propria TG2-specific IgA+ plasma cells occurs in gut-associated lymphoid tissues. The findings demonstrate immunogenicity of IEC-derived TG2-DGP fusion antigen supporting the notion of a pathogenic role for luminal TG2 in driving anti-TG2 autoimmunity in celiac disease.
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BibTeX
@misc{loberg2026role,
title = {{Role of gut epithelial-cell derived transglutaminase 2 in the formation of celiac disease autoantibodies}},
author = {R. I. Loberg and H. A. Abdi-Dezfuli and L. Kleppa and A. E. Dewan and M. T. Meling and L. M. Sollid and M. F. du Pre},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.01.748464},
url = {https://www.biorxiv.org/content/10.64898/2026.09.01.748464v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Role of gut epithelial-cell derived transglutaminase 2 in the formation of celiac disease autoantibodies
AU - R. I. Loberg
AU - H. A. Abdi-Dezfuli
AU - L. Kleppa
AU - A. E. Dewan
AU - M. T. Meling
AU - L. M. Sollid
AU - M. F. du Pre
PY - 2026
DA - 2026/09/01
PB - bioRxiv
DO - 10.64898/2026.09.01.748464
UR - https://www.biorxiv.org/content/10.64898/2026.09.01.748464v1
AB - 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 (DGP) containing a T-cell epitope. Upon induction, the TG2-DGP fusion protein was expressed in IECs and released into the intestinal lumen. In HLA-DQ2.5 transgenic mice with activated gluten-specific CD4+ T cells and naive TG2-specific B cells, expression of TG2-DGP was immunogenic and drove the production of intestinal and systemic anti-TG2 autoantibodies. TG2-specific B cells predominantly expanded in Peyers patches, suggesting that their priming and subsequent differentiation into lamina propria TG2-specific IgA+ plasma cells occurs in gut-associated lymphoid tissues. The findings demonstrate immunogenicity of IEC-derived TG2-DGP fusion antigen supporting the notion of a pathogenic role for luminal TG2 in driving anti-TG2 autoimmunity in celiac disease.
ER -