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

Kapur, Rick; Kim, Michael; Aslam, Rukhsana; McVey, Mark J; Tabuchi, Arata; Luo, Alice; Liu, Jonathan; Li, Yuan; Shanmugabhavananthan, Shanjeevan; Speck, Edwin R; Zufferey, Anne; Yousef, George; Zhang, Haibo; Rondina, Matthew T; Weyrich, Andrew S; Porcelijn, Leendert; Kuebler, Wolfgang M; Slutsky, Arthur S; Semple, John W.
Blood; 129(18): 2557-2569, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28202460
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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