title: T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10.
abstract: Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related fatalities and is characterized by acute respiratory distress following blood transfusion. Donor antibodies are frequently involved; however, the pathogenesis and protective mechanisms in the recipient are poorly understood, and specific therapies are lacking. Using newly developed murine TRALI models based on injection of anti-major histocompatibility complex class I antibodies, we found CD4+CD25+FoxP3+T regulatory cells (Tregs) and CD11c+dendritic cells (DCs) to be critical effectors that protect against TRALI. Treg or DC depletion in vivo resulted in aggravated antibody-mediated acute lung injury within 90 minutes with 60% mortality upon DC depletion. In addition, resistance to antibody-mediated TRALI was associated with increased interleukin-10 (IL-10) levels, and IL-10 levels were found to be decreased in mice suffering from TRALI. Importantly, IL-10 injection completely prevented and rescued the development of TRALI in mice and may prove to be a promising new therapeutic approach for alleviating lung injury in this serious complication of transfusion.
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.|Canadian Blood Services, Toronto, ON, Canada.
authors.forename: Rick
authors.initials: R
authors.lastname: Kapur
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Kim
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Rukhsana
authors.initials: R
authors.lastname: Aslam
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.|Canadian Blood Services, Toronto, ON, Canada.|Department of Anesthesia.|Department of Medicine, and.|Department of Physiology, University of Toronto, Toronto, ON, Canada.|Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McVey
authors.affiliation: Keenan Research Centre for Biomedical Science and.
authors.forename: Arata
authors.initials: A
authors.lastname: Tabuchi
authors.affiliation: Keenan Research Centre for Biomedical Science and.|Department of Anesthesia.|Department of Medicine, and.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Alice
authors.initials: A
authors.lastname: Luo
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Liu
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.|Department of Intensive Care, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Shanjeevan
authors.initials: S
authors.lastname: Shanmugabhavananthan
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Speck
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: Anne
authors.initials: A
authors.lastname: Zufferey
authors.affiliation: Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON, Canada.
authors.forename: George
authors.initials: G
authors.lastname: Yousef
authors.affiliation: Keenan Research Centre for Biomedical Science and.|Department of Anesthesia.|Department of Medicine, and.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Haibo
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Molecular Medicine Program and.|Department of Internal Medicine, University of Utah, Salt Lake City, UT.|Department of Internal Medicine, George E. Wahlen Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Rondina
authors.affiliation: Program in Molecular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT.
authors.forename: Andrew S
authors.initials: AS
authors.lastname: Weyrich
authors.affiliation: Department of Thrombocyte and Leukocyte Serology, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
authors.forename: Leendert
authors.initials: L
authors.lastname: Porcelijn
authors.affiliation: Keenan Research Centre for Biomedical Science and.|Department of Surgery and.|Department of Physiology, University of Toronto, Toronto, ON, Canada.|Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany.|German Heart Institute, Berlin, Germany.
authors.forename: Wolfgang M
authors.initials: WM
authors.lastname: Kuebler
authors.affiliation: Keenan Research Centre for Biomedical Science and.|Interdepartmental Division of Critical Care Medicine.
authors.forename: Arthur S
authors.initials: AS
authors.lastname: Slutsky
authors.affiliation: Keenan Research Centre for Biomedical Science and.|The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.|Canadian Blood Services, Toronto, ON, Canada.|Department of Pharmacology.|Department of Medicine, and.|Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; and.|Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden.
authors.forename: John W
authors.initials: JW
authors.lastname: Semple
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000276:immunology / Q000517:prevention & control; D000818:Animals; D000906:Antibodies / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology; D016753:Interleukin-10 / Q000276:immunology / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D065227:Transfusion Reaction
chemical_list: D000906:Antibodies; C556062:IL10 protein, mouse; D016753:Interleukin-10