T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10.
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| 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.
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| Authors | Rick Kapur, Michael Kim, Rukhsana Aslam, Mark J McVey, Arata Tabuchi, Alice Luo, Jonathan Liu, Yuan Li, Shanjeevan Shanmugabhavananthan, Edwin R Speck, Anne Zufferey, George Yousef, Haibo Zhang, Matthew T Rondina, Andrew S Weyrich, Leendert Porcelijn, Wolfgang M Kuebler, Arthur S Slutsky, John W Semple |
| Journal | Blood (Blood) Vol. 129 Issue 18 Pg. 2557-2569 (05 04 2017) ISSN: 1528-0020 [Electronic] United States |
| PMID | 28202460 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural) |
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