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Blood. 2017 May 4;129(18):2557-2569. doi: 10.1182/blood-2016-12-758185. Epub 2017 Feb 15.

T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10.

Kapur R1,2,3, Kim M1,2, Aslam R1,2, McVey MJ1,2,3,4,5,6,7, Tabuchi A1, Luo A1,4,5,6, Liu J1,2, Li Y1,2,8, Shanmugabhavananthan S1,2, Speck ER1,2, Zufferey A1,2, Yousef G9, Zhang H1,4,5,6, Rondina MT10,11,12, Weyrich AS13, Porcelijn L14, Kuebler WM1,15,6,16,17, Slutsky AS1,18, Semple JW1,2,3,19,5,20,21.

Author information

1
Keenan Research Centre for Biomedical Science and.
2
The Toronto Platelet Immunobiology Group, St. Michael's Hospital, Toronto, ON, Canada.
3
Canadian Blood Services, Toronto, ON, Canada.
4
Department of Anesthesia.
5
Department of Medicine, and.
6
Department of Physiology, University of Toronto, Toronto, ON, Canada.
7
Department of Anesthesia and Pain Medicine, The Hospital for Sick Children, Toronto, ON, Canada.
8
Department of Intensive Care, Qilu Hospital, Shandong University, Jinan, China.
9
Department of Laboratory Medicine, St. Michael's Hospital, Toronto, ON, Canada.
10
Molecular Medicine Program and.
11
Department of Internal Medicine, University of Utah, Salt Lake City, UT.
12
Department of Internal Medicine, George E. Wahlen Salt Lake City Veterans Affairs Medical Center, Salt Lake City, UT.
13
Program in Molecular Medicine, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT.
14
Department of Thrombocyte and Leukocyte Serology, Sanquin Diagnostic Services, Amsterdam, The Netherlands.
15
Department of Surgery and.
16
Institute of Physiology, Charité-Universitätsmedizin, Berlin, Germany.
17
German Heart Institute, Berlin, Germany.
18
Interdepartmental Division of Critical Care Medicine.
19
Department of Pharmacology.
20
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada; and.
21
Division of Hematology and Transfusion Medicine, Lund University, Lund, Sweden.

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.

PMID:
28202460
PMCID:
PMC5418638
DOI:
10.1182/blood-2016-12-758185
[Indexed for MEDLINE]
Free PMC Article

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