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

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

doi:10.1182/blood-2016-12-758185

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

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

Research output: Contribution to journal › Article › peer-review

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.

Original language	English
Pages (from-to)	2557-2569
Number of pages	13
Journal	Blood
Volume	129
Issue number	18
DOIs	https://doi.org/10.1182/blood-2016-12-758185
Publication status	Published - 2017

Subject classification (UKÄ)

Immunology in the medical area

Free keywords

Acute Lung Injury
Animals
Antibodies
Dendritic Cells
Interleukin-10
Mice
Mice, Inbred BALB C
Mice, Knockout
T-Lymphocytes, Regulatory
Transfusion Reaction
Journal Article

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10.1182/blood-2016-12-758185

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Kapur, R., Kim, M., Aslam, R., McVey, M. J., Tabuchi, A., Luo, A., Liu, J., Li, Y., Shanmugabhavananthan, S., Speck, E. R., Zufferey, A., Yousef, G., Zhang, H., Rondina, M. T., Weyrich, A. S., Porcelijn, L., Kuebler, W. M., Slutsky, A. S., & Semple, J. W. (2017). T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10. Blood, 129(18), 2557-2569. https://doi.org/10.1182/blood-2016-12-758185

@article{89f9ca8a4fc549cfb026af0a680807cb,

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

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.",

keywords = "Acute Lung Injury, Animals, Antibodies, Dendritic Cells, Interleukin-10, Mice, Mice, Inbred BALB C, Mice, Knockout, T-Lymphocytes, Regulatory, Transfusion Reaction, Journal Article",

author = "Rick Kapur and Michael Kim and Rukhsana Aslam and McVey, {Mark J} and Arata Tabuchi and Alice Luo and Jonathan Liu and Yuan Li and Shanjeevan Shanmugabhavananthan and Speck, {Edwin R} and Anne Zufferey and George Yousef and Haibo Zhang and Rondina, {Matthew T} and Weyrich, {Andrew S} and Leendert Porcelijn and Kuebler, {Wolfgang M} and Slutsky, {Arthur S} and Semple, {John W}",

year = "2017",

doi = "10.1182/blood-2016-12-758185",

language = "English",

volume = "129",

pages = "2557--2569",

journal = "Blood",

issn = "1528-0020",

publisher = "American Society of Hematology",

number = "18",

}

Kapur, R, Kim, M, Aslam, R, McVey, MJ, Tabuchi, A, Luo, A, Liu, J, Li, Y, Shanmugabhavananthan, S, Speck, ER, Zufferey, A, Yousef, G, Zhang, H, Rondina, MT, Weyrich, AS, Porcelijn, L, Kuebler, WM, Slutsky, AS & Semple, JW 2017, 'T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10', Blood, vol. 129, no. 18, pp. 2557-2569. https://doi.org/10.1182/blood-2016-12-758185

TY - JOUR

T1 - T regulatory cells and dendritic cells protect against transfusion-related acute lung injury via IL-10

AU - Kapur, Rick

AU - Kim, Michael

AU - Aslam, Rukhsana

AU - McVey, Mark J

AU - Tabuchi, Arata

AU - Luo, Alice

AU - Liu, Jonathan

AU - Li, Yuan

AU - Shanmugabhavananthan, Shanjeevan

AU - Speck, Edwin R

AU - Zufferey, Anne

AU - Yousef, George

AU - Zhang, Haibo

AU - Rondina, Matthew T

AU - Weyrich, Andrew S

AU - Porcelijn, Leendert

AU - Kuebler, Wolfgang M

AU - Slutsky, Arthur S

AU - Semple, John W

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Acute Lung Injury

KW - Animals

KW - Antibodies

KW - Dendritic Cells

KW - Interleukin-10

KW - Mice

KW - Mice, Inbred BALB C

KW - Mice, Knockout

KW - T-Lymphocytes, Regulatory

KW - Transfusion Reaction

KW - Journal Article

U2 - 10.1182/blood-2016-12-758185

DO - 10.1182/blood-2016-12-758185

M3 - Article

C2 - 28202460

SN - 1528-0020

VL - 129

SP - 2557

EP - 2569

JO - Blood

JF - Blood

IS - 18

ER -

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

Abstract

Subject classification (UKÄ)

Free keywords

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