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

Moretti, Alex
Marinoni, Maddalena
Agosti, Massimo
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Published in Cell reports. 2022, vol. 39, no. 11, 110956
Abstract Celiac disease (CD) is a multisystem disease in which different organs may be affected. We investigate whether circulating innate lymphoid cells (ILCs) contribute to the CD peripheral inflammatory status. We find that the CD cytokine profile is characterized by high concentrations of IL-12p40, IL-18, and IFN-γ, paralleled by an expansion of ILC precursors (ILCPs). In the presence of the gliadin peptides p31-43 and pα-9, ILCPs from CD patients increase transglutaminase 2 (TG2) expression, produce IL-18 and IFN-γ, and stimulate CD4+T lymphocytes. IFN-γ 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-γ and ILCP presence and mark the CD population mostly affected by extraintestinal symptoms. Dietary vitamin D supplementation appears to be an interesting therapeutic approach to dampen ILCP-mediated IFN-γ production.
Keywords CP: ImmunologyIFN-γIL-12IL-18ILCPsILCsCeliac diseaseExtraintestinal symptomsGliadinGluten peptidesInnate lymphoid cellsVitamin DCeliac DiseaseGliadin / metabolismHumansImmunity, InnateInterleukin-12 Subunit p40 / metabolismInterleukin-18 / metabolismIntestinal Mucosa / metabolismLymphocytes / metabolismVitamin D / metabolismVitamin D / pharmacology
PMID: 35705047
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Research group Ciblage des lymphocytes sécrétant des cytokines (1015)
Swiss National Science Foundation: PZ00P3_161459
Swiss National Science Foundation: PR00P3_179727
(ISO format)
ERCOLANO, Giuseppe et al. Gliadin-reactive vitamin D-sensitive proinflammatory ILCPs are enriched in celiac patients. In: Cell reports, 2022, vol. 39, n° 11, p. 110956. doi: 10.1016/j.celrep.2022.110956 https://archive-ouverte.unige.ch/unige:161600

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Deposited on : 2022-06-22

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