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

Kapur, Rick LU ; Kim, Michael; Aslam, Rukhsana; McVey, Mark J; Tabuchi, Arata; Luo, Alice; Liu, Jonathan; Li, Yuan; Shanmugabhavananthan, Shanjeevan and Speck, Edwin R, et al. (2017) In Blood 129(18). p.2557-2569
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... (More)

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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keywords
Acute Lung Injury, Animals, Antibodies, Dendritic Cells, Interleukin-10, Mice, Mice, Inbred BALB C, Mice, Knockout, T-Lymphocytes, Regulatory, Transfusion Reaction, Journal Article
in
Blood
volume
129
issue
18
pages
13 pages
publisher
American Society of Hematology
external identifiers
  • scopus:85020165674
  • wos:000400555800015
ISSN
1528-0020
DOI
10.1182/blood-2016-12-758185
language
English
LU publication?
yes
id
89f9ca8a-4fc5-49cf-b026-af0a680807cb
date added to LUP
2017-12-21 11:32:37
date last changed
2018-05-20 04:39:35
@article{89f9ca8a-4fc5-49cf-b026-af0a680807cb,
  abstract     = {<p>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.</p>},
  author       = {Kapur, Rick and Kim, Michael and Aslam, Rukhsana and McVey, Mark J and Tabuchi, Arata and Luo, Alice and Liu, Jonathan and Li, Yuan and Shanmugabhavananthan, Shanjeevan and Speck, Edwin R and Zufferey, Anne and Yousef, George and Zhang, Haibo and Rondina, Matthew T and Weyrich, Andrew S and Porcelijn, Leendert and Kuebler, Wolfgang M and Slutsky, Arthur S and Semple, John W},
  issn         = {1528-0020},
  keyword      = {Acute Lung Injury,Animals,Antibodies,Dendritic Cells,Interleukin-10,Mice,Mice, Inbred BALB C,Mice, Knockout,T-Lymphocytes, Regulatory,Transfusion Reaction,Journal Article},
  language     = {eng},
  number       = {18},
  pages        = {2557--2569},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10},
  url          = {http://dx.doi.org/10.1182/blood-2016-12-758185},
  volume       = {129},
  year         = {2017},
}