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T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10
Ist Teil von
Blood, 2017-05, Vol.129 (18), p.2557-2569
Ort / Verlag
United States: Elsevier Inc
Erscheinungsjahr
2017
Quelle
MEDLINE
Beschreibungen/Notizen
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.
•CD4+CD25+FoxP3+ T regulatory cells and CD11c+ dendritic cells protect against antibody-mediated murine TRALI.•Murine TRALI is associated with reduced IL-10 levels, and IL-10 administration prevents and rescues TRALI development.