title: Interleukin 10 receptor signaling: master regulator of intestinal mucosal homeostasis in mice and humans.
abstract: Interleukin 10 (IL10) is a key anti-inflammatory cytokine that can inhibit proinflammatory responses of both innate and adaptive immune cells. An association between IL10 and intestinal mucosal homeostasis became clear with the discovery that IL10 and IL10 receptor (IL10R)-deficient mice develop spontaneous intestinal inflammation. Similarly, patients with deleterious mutations in IL10, IL10RA, or IL10RB present with severe enterocolitis within the first months of life. Here, we review recent findings on how IL10- and IL10R-dependent signaling modulates innate and adaptive immune responses in the murine gastrointestinal tract, with implications of their role in the prevention of inflammatory bowel disease (IBD). In addition, we discuss the impact of IL10 and IL10R signaling defects in humans and their relationship to very early-onset IBD (VEO-IBD).
authors: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Dror S
authors: DS
authors: Shouval
authors: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Jodie
authors: J
authors: Ouahed
authors: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Amlan
authors: A
authors: Biswas
authors: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Jeremy A
authors: JA
authors: Goettel
authors: Division of Emergency Medicine, Boston Children's Hospital, Boston, Massachusetts, USA.
authors: Bruce H
authors: BH
authors: Horwitz
authors: Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, Munich, Germany.
authors: Christoph
authors: C
authors: Klein
authors: Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada; Program in Cell Biology at University of Toronto, Toronto, Ontario, Canada.
authors: Aleixo M
authors: AM
authors: Muise
authors: Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA; Division of Gastroenterology, Brigham & Women's Hospital, Boston, Massachusetts, USA. Electronic address: scott.snapper@childrens.harvard.edu.
authors: Scott B
authors: SB
authors: Snapper
mesh_terms: D056704:Adaptive Immunity / Q000235:genetics; D000818:Animals; D004760:Enterocolitis / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D015212:Inflammatory Bowel Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D007413:Intestinal Mucosa / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D053701:Receptors, Interleukin-10 / Q000172:deficiency / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology*
chemical_list: D053701:Receptors, Interleukin-10
keywords: Colitis; IBD; IL10; IL10 receptor; Microbiome; Very early-onset IBD