Gliadin-reactive vitamin D-sensitive proinflammatory ILCPs are enriched in celiac patients

Summary

Celiac disease (CD) is a multisystem disease in which different organs may be affected. The authors of this article published in Cell Reports, led by Prof Camilla Jandus, a member of the Geneva Centre for Inflammation Research, and Dr Sara Trabanelli, scientific collaborator in the same team, investigated whether circulating innate lymphoid cells (ILCs) contribute to the CD peripheral inflammatory status. The authors found that the CD cytokine profile is characterized by high concentrations of IL-12p40, IL-18, and IFN-g, paralleled by an expansion of ILC precursors (ILCPs). In the presence of the gliadin peptides p31–43 and pa-9, ILCPs from CD patients increase transglutaminase 2 (TG2) expression, produce IL-18 and IFN-g, and stimulate CD4+ T lymphocytes. IFN-g is also produced upon stimulation with IL-12p40 and IL-18 and is inhibited by the addition of vitamin D. Low levels of blood vitamin D correlate with high IFN-g and ILCP presence and mark the CD population mostly affected by extraintestinal symptoms. The researchers conclude that dietary vitamin D supplementation appears to be an interesting therapeutic approach to dampening ILCP-mediated IFN-g production.

Read full article: doi.org/10.1016/j.celrep.2022.110956

Why is this study important?

The authors show how activation of specific innate cells called ILCP with gluten-derived peptides, namely gliadin peptides, in children with coeliac disease (CD), contributes to extraintestinal peripheral inflammation. ILCP activation is reduced by vitamin D, which is low in patients who experience severe systemic inflammation and show more extraintestinal symptoms. Since vitamin D deficiency is a hallmark of CD, their data suggest that, together with a gluten-free diet, the benefits of vitamin D supplementation should be further explored and could be highly beneficial and relevant to reduce or even suppress chronic peripheral inflammation that can induce clinical complications or favour other autoimmune diseases.

This work was supported by the SNF, the Helmut Horten Foundation, the Bourse Pro-Femmes University of Lausanne, and Fondazione Umberto Veronesi.

News