Autophagy gene Atg16L1 prevents lethal T cell alloreactivity mediated by dendritic cells.

Autor: Hubbard-Lucey VM; Kimmel Center for Biology and Medicine at the Skirball Institute, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA., Shono Y; Department of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Maurer K; Kimmel Center for Biology and Medicine at the Skirball Institute, New York, NY 10016, USA; Sackler Institute of Graduate Biomedical Sciences, New York University School of Medicine, New York, NY 10016, USA., West ML; Department of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Singer NV; Department of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Ziegler CG; Department of Computational Biology and Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA., Lezcano C; Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Motta AC; Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Schmid K; Department of Haematology and Oncology, University Medical Centre University of Regensburg, Regensburg, 93053, Germany., Levi SM; Department of Chemistry, University of Pennsylvania, Philadelphia, PA, 19104, USA., Murphy GF; Program in Dermatopathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA., Liu C; Department of Pathology, Immunology and Laboratory Medicine, University of Florida College of Medicine, Gainesville, FL 32611, USA., Winkler JD; Department of Chemistry, University of Pennsylvania, Philadelphia, PA, 19104, USA; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA., Amaravadi RK; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA 19104, USA; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA., Rogler G; Department of Gastroenterology, University Hospital Zürich, Rämistrasse 100, 8006 Zurich, Switzerland., Dickinson AM; Haematological Sciences, Institute of Cellular Medicine, Newcastle University, NE2 4HH Tyne and Wear, UK., Holler E; Department of Haematology and Oncology, University Medical Centre University of Regensburg, Regensburg, 93053, Germany., van den Brink MR; Department of Immunology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA. Electronic address: vandenbm@mskcc.org., Cadwell K; Kimmel Center for Biology and Medicine at the Skirball Institute, New York, NY 10016, USA; Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA. Electronic address: ken.cadwell@med.nyu.edu.
Jazyk: angličtina
Zdroj: Immunity [Immunity] 2014 Oct 16; Vol. 41 (4), pp. 579-91. Date of Electronic Publication: 2014 Oct 09.
DOI: 10.1016/j.immuni.2014.09.011
Abstrakt: Atg16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with inflammatory bowel disease. Here we find that Atg16L1 deficiency leads to an exacerbated graft-versus-host disease (GVHD) in a mouse model of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Atg16L1-deficient allo-HSCT recipients with GVHD displayed increased T cell proliferation due to increased dendritic cell (DC) numbers and costimulatory molecule expression. Reduced autophagy within DCs was associated with lysosomal abnormalities and decreased amounts of A20, a negative regulator of DC activation. These results broaden the function of Atg16L1 and the autophagy pathway to include a role in limiting a DC-mediated response during inflammatory disease, such as GVHD.
Databáze: MEDLINE