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Interleukin-10 receptor signaling in innate immune cells regulates mucosal immune tolerance and anti-inflammatory macrophage function.
Shouval, Dror S; Biswas, Amlan; Goettel, Jeremy A; McCann, Katelyn; Conaway, Evan; Redhu, Naresh S; Mascanfroni, Ivan D; Al Adham, Ziad; Lavoie, Sydney; Ibourk, Mouna; Nguyen, Deanna D; Samsom, Janneke N; Escher, Johanna C; Somech, Raz; Weiss, Batia; Beier, Rita; Conklin, Laurie S; Ebens, Christen L; Santos, Fernanda G M S; Ferreira, Alexandre R; Sherlock, Mary; Bhan, Atul K; Müller, Werner; Mora, J Rodrigo; Quintana, Francisco J; Klein, Christoph; Muise, Aleixo M; Horwitz, Bruce H; Snapper, Scott B.
Afiliação
  • Shouval DS; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Biswas A; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Goettel JA; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • McCann K; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Conaway E; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Redhu NS; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Mascanfroni ID; Center of Neurological Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Al Adham Z; Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada.
  • Lavoie S; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
  • Ibourk M; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA.
  • Nguyen DD; Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Samsom JN; Laboratory of Pediatric Gastroenterology, Erasmus Medical Center-Sophia Children's Hospital, 3000 CA Rotterdam, the Netherlands; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Escher JC; Department of Pediatrics, Erasmus Medical Center-Sophia Children's Hospital, 3000 CA Rotterdam, the Netherlands; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Somech R; Pediatric Immunology Service, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52661, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Weiss B; Division of Pediatric Gastroenterology and Nutrition, Edmond and Lily Safra Children's Hospital, Sheba Medical Center, Tel Hashomer 52661, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Beier R; Department of Pediatric Hematology and Oncology, Hannover Medical School, 30625 Hannover, Germany; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Conklin LS; Department of Gastroenterology, Children's National Medical Center, Washington, D.C. 20010, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Ebens CL; Division of Pediatric Hematology and Oncology, University of Michigan, Ann Arbor, MI 48109, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Santos FG; Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Ferreira AR; Hospital das Clínicas, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais 30130-100, Brazil; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Sherlock M; Division of Gastroenterology, McMaster Children's Hospital, West Hamilton, Ontario L8N 3Z5, Canada; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Bhan AK; Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
  • Müller W; Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK.
  • Mora JR; Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA 02114, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Quintana FJ; Center of Neurological Diseases, Brigham and Women's Hospital, Boston, MA 02115, USA.
  • Klein C; Dr von Hauner Children's Hospital, Ludwig-Maximilians-University, 80337 Munich, Germany; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Muise AM; Division of Gastroenterology, Hepatology, and Nutrition, Department of Paediatrics, Hospital for Sick Children, Toronto, Ontario M5G 1X8, Canada; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Horwitz BH; Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA; Department of Pathology, Brigham and Women's Hospital, Boston, MA 02115, USA; interNational Early Onset Paediatric IBD Cohort Study (NEOPICS).
  • Snapper SB; Division of Gastroenterology, Hepatology and Nutrition, Boston Children's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA; Division of Gastroenterology, Brigham and Women's Hospital, Boston, MA 02115, USA; interNational Early Onset Paediatric IB
Immunity ; 40(5): 706-19, 2014 May 15.
Article em En | MEDLINE | ID: mdl-24792912
ABSTRACT
Intact interleukin-10 receptor (IL-10R) signaling on effector and T regulatory (Treg) cells are each independently required to maintain immune tolerance. Here we show that IL-10 sensing by innate immune cells, independent of its effects on T cells, was critical for regulating mucosal homeostasis. Following wild-type (WT) CD4(+) T cell transfer, Rag2(-/-)Il10rb(-/-) mice developed severe colitis in association with profound defects in generation and function of Treg cells. Moreover, loss of IL-10R signaling impaired the generation and function of anti-inflammatory intestinal and bone-marrow-derived macrophages and their ability to secrete IL-10. Importantly, transfer of WT but not Il10rb(-/-) anti-inflammatory macrophages ameliorated colitis induction by WT CD4(+) T cells in Rag2(-/-)Il10rb(-/-) mice. Similar alterations in the generation and function of anti-inflammatory macrophages were observed in IL-10R-deficient patients with very early onset inflammatory bowel disease. Collectively, our studies define innate immune IL-10R signaling as a key factor regulating mucosal immune homeostasis in mice and humans.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Colite Ulcerativa / Interleucina-10 / Receptores de Interleucina-10 Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
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XML
PubMed Links
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Colite Ulcerativa / Interleucina-10 / Receptores de Interleucina-10 Idioma: En Ano de publicação: 2014 Tipo de documento: Article