Biomaterial Database

IL-10-producing regulatory cells impact on celiac disease evolution. 2024

Laura Passerini, and Giada Amodio, and Virginia Bassi, and Serena Vitale, and Ilaria Mottola, and Marina Di Stefano, and Lorella Fanti, and Paola Sgaramella, and Chiara Ziparo, and Silvia Furio, and Renata Auricchio, and Graziano Barera, and Giovanni Di Nardo, and Riccardo Troncone, and Carmen Gianfrani, and Silvia Gregori

Mechanisms of Peripheral Tolerance Unit, San Raffaele Telethon Institute for Gene Therapy (SR-Tiget), IRCCS San Raffaele Scientific Institute, Via Olgettina 60, Milan 20132, Italy.

Celiac Disease (CD) is a T-cell mediated disorder caused by immune response to gluten, although the mechanisms underlying CD progression are still elusive. We analyzed immune cell composition, plasma cytokines, and gliadin-specific T-cell responses in patients with positive serology and normal intestinal mucosa (potential-CD) or villous atrophy (acute-CD), and after gluten-free diet (GFD). We found: an inflammatory signature and the presence of circulating gliadin-specific IFN-γ+ T cells in CD patients regardless of mucosal damage; an increased frequency of IL-10-secreting dendritic cells (DC-10) in the gut and of circulating gliadin-specific IL-10-secreting T cells in potential-CD; IL-10 inhibition increased IFN-γ secretion by gliadin-specific intestinal T cells from acute- and potential-CD. On GFD, inflammatory cytokines normalized, while IL-10-producing T cells accumulated in the gut. We show that IL-10-producing cells are fundamental in controlling pathological T-cell responses to gluten: DC-10 protect the intestinal mucosa from damage and represent a marker of potential-CD.