Funding

In April 2024, the ISSCD in collaboration with the Celiac Disease Foundation, announced a Fellowship award up to the value of 300,000 USD.

There were six strong applications to this call, and each was reviewed by three peer reviewers, all members of the ISSCD. All proposals were considered suitable for funding but taking into consideration all individual scores and comments, the grant was awarded to Dr Fleur du Pré at the Oslo University Hospital for a project titled ‘B-cell T-cell cross talk in celiac disease’.

“I'm honoured to be awarded the research fellowship and would like to thank the celiac foundation and ISSCD for this great opportunity to continue my research on celiac disease. I look forward to sharing the results with the community!”

The project will aim to investigate where the cross talk between T cells and B cells in celiac disease takes place, and where enzymatically active TG2 (a cytosolic protein) encounters gluten peptides for deamidation and the formation TG2-gluten complexes that facilitate the collaboration between B cells and T cells.

It is well accepted that the cross talk between B cells and T cells drives chronic inflammation in a range of autoimmune diseases, such as rheumatoid arthritis, multiple sclerosis and systemic lupus erythematosus. B-cell depletion therapy, which disrupts B-cell T-cell collaboration is very successful at treating these autoimmune conditions.

In celiac disease, inflammatory CD4+ T cells recognize deamidated gluten peptides bound to the disease-predisposing molecules HLA-DQ2 or HLA-DQ8. The generation of deamidated gluten epitopes is catalysed by TG2 and results in stronger responses of gluten-specific T cells. During the deamidation reaction, enzyme-substrate intermediate complexes of TG2-gluten are formed. These TG2-gluten complexes bind to the B-cell receptor of TG2-specific B cells, allowing the B cells to present a gluten peptide to gluten-specific CD4+ T cells and thereby receiving the required T-cell help for antibody production. At the same time, this B-cell T-cell cross talk causes the proliferation and clonal expansion of the T cells and is thus equally important to augment the anti-gluten T-cell response.

It is hypothesized that TG2 encounters gluten already in the gut lumen, and that TG2-specific B cells and gluten-specific T cells interact in gut-associated lymphoid tissue, comprising Peyer’s patches and isolated lymphoid follicles, following the uptake of TG2-gluten complexes

from the gut lumen. This hypothesis is supported by recent evidence that the small intestinal lumen in mice contains catalytically active TG2 (derived from shed enterocytes).

This project aims to identify where gluten peptides become deamidated and where TG2-specific B cells are activated to become autoantibody producing plasma cells. It hopes to identify new targets for treatments.

A huge congratulations to Fleur on behalf of the board! The ISSCD would like to express appreciation to all the applicants who took the time to prepare their submissions, and strongly encourages future applications. The ISSCD also extends our sincere gratitude to the peer reviewers and wishes Fleur all the very best in the delivery of her research.