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

被引：107

作者：

Kapur, Rick ^{[1
,2
,3
]}

Kim, Michael ^{[1
,2
]}

Aslam, Rukhsana ^{[1
,2
]}

McVey, Mark J. ^{[1
,2
,3
,4
,5
,6
,7
]}

Tabuchi, Arata ^{[1
]}

Luo, Alice ^{[1
,4
,5
,6
]}

Liu, Jonathan ^{[1
,2
]}

Li, Yuan ^{[1
,2
,8
]}

Shanmugabhavananthan, Shanjeevan ^{[1
,2
]}

Speck, Edwin R. ^{[1
,2
]}

Zufferey, Anne ^{[1
,2
,22
]}

Yousef, George ^{[9
]}

Zhang, Haibo ^{[1
,4
,5
,6
]}

Rondina, Matthew T. ^{[10
,11
,12
]}

Weyrich, Andrew S. ^{[13
]}

Porcelijn, Leendert ^{[14
]}

Kuebler, Wolfgang M. ^{[1
,6
,15
,16
,17
]}

Slutsky, Arthur S. ^{[1
,18
]}

Semple, John W. ^{[1
,2
,3
,5
,19
,20
,21
]}

机构：

[1] St Michaels Hosp, Keenan Res Ctr Biomed Sci, Toronto, ON, Canada

[2] St Michaels Hosp, Toronto Platelet Immunobiol Grp, Toronto, ON, Canada

[3] Canadian Blood Serv, Toronto, ON, Canada

[4] Univ Toronto, Dept Anesthesia, Toronto, ON, Canada

[5] Univ Toronto, Dept Med, Toronto, ON, Canada

[6] Univ Toronto, Dept Physiol, Toronto, ON, Canada

[7] Hosp Sick Children, Dept Anesthesia & Pain Med, Toronto, ON, Canada

[8] Shandong Univ, Qilu Hosp, Dept Intens Care, Jinan, Peoples R China

[9] St Michaels Hosp, Dept Lab Med, Toronto, ON, Canada

[10] Univ Utah, Program Mol Med, Salt Lake City, UT USA

[11] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA

[12] George E Wahlen Salt Lake City Vet Affairs Med Ct, Dept Internal Med, Salt Lake City, UT USA

[13] Univ Utah, Sch Med, Dept Internal Med, Program Mol Med, Salt Lake City, UT USA

[14] Sanquin Diagnost Serv, Dept Thrombocyte & Leukocyte Serol, Amsterdam, Netherlands

[15] Univ Toronto, Dept Surg, Toronto, ON, Canada

[16] Charite, Inst Physiol, Berlin, Germany

[17] German Heart Inst, Berlin, Germany

[18] Univ Toronto, Interdept Div Crit Care Med, Toronto, ON, Canada

[19] Univ Toronto, Dept Pharmacol, Toronto, ON, Canada

[20] Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada

[21] Lund Univ, Div Hematol & Transfus Med, Lund, Sweden

[22] CHUL UL, Ctr Rech, CHU Quebec, Quebec City, PQ, Canada

来源：

BLOOD | 2017年 / 129卷 / 18期

基金：

瑞士国家科学基金会; 美国国家卫生研究院;

关键词：

NONCARDIOGENIC PULMONARY-EDEMA; FRESH-FROZEN PLASMA; CLASS-II ANTIBODIES; DONOR ANTIBODIES; BLOOD; RECIPIENT; TRALI; PATHOGENESIS; MOUSE; BACK;

D O I：

10.1182/blood-2016-12-758185

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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.

引用

页码：2557 / 2569

页数：13

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