title: Donor-derived exosomes induce specific regulatory T cells to suppress immune inflammation in the allograft heart.
abstract: To inhibit the immune inflammation in the allografts can be beneficial to organ transplantation. This study aims to induce the donor antigen specific regulatory T cells (Treg cell) inhibit the immune inflammation in the allograft heart. In this study, peripheral exosomes were purified from the mouse serum. A heart transplantation mouse model was developed. The immune inflammation of the allograft heart was assessed by histology and flow cytometry. The results showed that the donor antigen-specific T helper (Th)2 pattern inflammation was observed in the allograft hearts; the inflammation was inhibited by immunizing the recipient mice with the donor-derived exosomes. Purified peripheral exosomes contained integrin MMP1a; the latter induced CD4(+) T cells to express Fork head protein-3 and transforming growth factor (TGF)-β via inhibiting the Th2 transcription factor, GATA binding protein 3, in CD4(+) T cells. Administration with the donor-derived exosomes significantly prolonged the allograft heart survival. We conclude that the donor-derived peripheral exosomes have the capacity to inhibit the immune inflammation in the allograft heart via inducing specific Treg cells, implicating that administration with the donor-derived exosomes may be beneficial to cardiac transplantation.
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Jiangping
authors.initials: J
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Teng
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Zhizhao
authors.initials: Z
authors.lastname: Song
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Xing
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Mangyuan
authors.initials: M
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Pingchang
authors.initials: P
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, 167A Beilishi Road, Xi Cheng District, Beijing, 100037, China.
authors.forename: Shengshou
authors.initials: S
authors.lastname: Hu
mesh_terms: D064591:Allografts / Q000276:immunology; D000818:Animals; D000941:Antigens / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D055354:Exosomes / Q000276:immunology* / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology; D016027:Heart Transplantation; D007108:Immune Tolerance; D007249:Inflammation / Q000276:immunology* / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000276:immunology; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014019:Tissue Donors
chemical_list: D000941:Antigens; D020781:Matrix Metalloproteinase 1; C425310:Mmp1a protein, mouse
references.citation: Tex Heart Inst J. 2013;40(4):395-9
references.pmid: 24082367
references.citation: Nat Immunol. 2008 Dec;9(12):1347-55
references.pmid: 18997793
references.citation: J Neuroimmunol. 2014 Nov 15;276(1-2):58-63
references.pmid: 25171813
references.citation: Am J Cardiol. 2015 Feb 15;115(4):499-504
references.pmid: 25554534
references.citation: Am J Cardiovasc Drugs. 2004;4(1):21-9
references.pmid: 14967063
references.citation: J Immunol. 2015 Mar 15;194(6):2899-908
references.pmid: 25687759
references.citation: Sci Rep. 2014;4:4649
references.pmid: 24721951
references.citation: J Allergy Clin Immunol. 2013 Jun;131(6):1644-52
references.pmid: 23632297
references.citation: Cytokine. 2012 Jul;59(1):59-64
references.pmid: 22579114
references.citation: Proc Natl Acad Sci U S A. 2014 Jan 14;111(2):711-6
references.pmid: 24379393
references.citation: Annu Rev Immunol. 2012;30:39-68
references.pmid: 22136167
references.citation: J Biol Chem. 2005 Jun 17;280(24):23243-50
references.pmid: 15826950
references.citation: J Immunol. 2006 Dec 15;177(12):8338-47
references.pmid: 17142730
references.citation: Front Immunol. 2014 Jul 15;5:333
references.pmid: 25076948
references.citation: Trends Immunol. 2013 Mar;34(3):107-13
references.pmid: 23228885
references.citation: Transplant Proc. 2014 May;46(4):1169-74
references.pmid: 24815153
references.citation: J Thorac Dis. 2014 Aug;6(8):1120-8
references.pmid: 25132979
references.citation: Transpl Int. 2014 May;27(5):e38-42
references.pmid: 24444397
references.citation: Cell Immunol. 2015 Jan;293(1):30-3
references.pmid: 25497973
references.citation: PLoS One. 2012;7(8):e44045
references.pmid: 22952868
references.citation: Transplantation. 1998 Apr 27;65(8):1115-23
references.pmid: 9583874
references.citation: J Thromb Thrombolysis. 2014 Jan;37(1):17-23
references.pmid: 24264961
references.citation: Mol Carcinog. 2014 Aug;53(8):659-66
references.pmid: 23475608
references.citation: Clin Transplant. 1994 Jun;8(3 Pt 2):313-8
references.pmid: 7520306
references.citation: J Mol Cell Biol. 2013 Dec;5(6):369-79
references.pmid: 24280647
references.citation: Sci Rep. 2014;4:7583
references.pmid: 25533220
references.citation: Semin Immunol. 2011 Dec;23(6):424-30
references.pmid: 22055883
references.citation: J Extracell Vesicles. 2014 Dec 22;3:26913
references.pmid: 25536934
references.citation: Nat Med. 2005 Jun;11(6):605-13
references.pmid: 15937473