IL-10-producing regulatory cells impact on celiac disease evolution
Laura Passerini, Giada Amodio, Virginia Bassi, Serena Vitale, Ilaria Mottola, Marina Di Stefano, Lorella Fanti, Paola Sgaramella, Chiara Ziparo, Silvia Furio, Renata Auricchio, Graziano Barera, Giovanni Di Nardo, Riccardo Troncone, Carmen Gianfrani, Silvia Gregori
Abstract
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.