title: Thrombospondin-1 (TSP1)-producing B cells restore antigen (Ag)-specific immune tolerance in an allergic environment.
abstract: Restoration of the antigen (Ag)-specific immune tolerance in an allergic environment is refractory. B cells are involved in immune regulation. Whether B cells facilitate the generation of Ag-specific immune tolerance in an allergic environment requires further investigation. This paper aims to elucidate the mechanism by which B cells restore the Ag-specific immune tolerance in an allergic environment. In this study, a B cell-deficient mouse model was created by injecting an anti-CD20 antibody. The frequency of tolerogenic dendritic cell (TolDC) was assessed by flow cytometry. The levels of cytokines were determined by enzyme-linked immunosorbent assay. The expression of thrombospondin-1 (TSP1) was assessed by quantitative real-time RT-PCR, Western blotting, and methylation-specific PCR. The results showed that B cells were required in the generation of the TGF-β-producing TolDCs in mice. B cell-derived TSP1 converted the latent TGF-β to the active TGF-β in DCs, which generated TGF-β-producing TolDCs. Exposure to IL-13 inhibited the expression of TSP1 in B cells by enhancing the TSP1 gene DNA methylation. Treating food allergy mice with Ag-specific immunotherapy and IL-13 antagonists restored the generation of TolDCs and enhanced the effect of specific immunotherapy. In conclusion, B cells play a critical role in the restoration of specific immune tolerance in an allergic environment. Blocking IL-13 in an allergic environment facilitated the generation of TolDCs and enhanced the therapeutic effect of immunotherapy.
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and Longgang Central Hospital, Shenzhen 518116, China.
authors.forename: Gui
authors.initials: G
authors.lastname: Yang
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and Longgang Central Hospital, Shenzhen 518116, China.
authors.forename: Xiao-Rui
authors.initials: XR
authors.lastname: Geng
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and Longgang Central Hospital, Shenzhen 518116, China.
authors.forename: Zhi-Qiang
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and Longgang Central Hospital, Shenzhen 518116, China.
authors.forename: Jiang-Qi
authors.initials: JQ
authors.lastname: Liu
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China.
authors.forename: Xiao-Yu
authors.initials: XY
authors.lastname: Liu
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China.
authors.forename: Ling-Zhi
authors.initials: LZ
authors.lastname: Xu
authors.affiliation: the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and.
authors.forename: Huan-Ping
authors.initials: HP
authors.lastname: Zhang
authors.affiliation: the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and.
authors.forename: Ying-Xue
authors.initials: YX
authors.lastname: Sun
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, lzg@szu.edu.cn.
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Liu
authors.affiliation: From the ENT Institute of Shenzhen University, Shenzhen Key Laboratory of Allergy and Immunology, Shenzhen University School of Medicine, and State Key Laboratory of Respiratory Disease for Allergy at Shenzhen University, Shenzhen University, Shenzhen 518060, China, the Brain Body Institute, McMaster University, Hamilton, Ontario L8N 4A6, Canada, and pcy2356@szu.edu.cn.
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Yang
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology; D019175:DNA Methylation / Q000187:drug effects* / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology / Q000473:pathology; D003888:Desensitization, Immunologic; D005512:Food Hypersensitivity / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D007108:Immune Tolerance / Q000187:drug effects* / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D019700:Thrombospondin 1 / Q000235:genetics / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology
chemical_list: D018793:Interleukin-13; D019700:Thrombospondin 1; D016212:Transforming Growth Factor beta; C585483:Thbs1 protein, mouse
keywords: B lymphocyte; allergy; cellular immune response; immunotherapy; interleukin; interleukin 13; intestine
references.citation: Autoimmunity. 2012 Aug;45(5):415-26
references.pmid: 22429146
references.citation: Adv Immunol. 2010;108:111-65
references.pmid: 21056730
references.citation: Gastroenterology. 2011 Jul;141(1):249-58, 258.e1-2
references.pmid: 21569774
references.citation: J Exp Med. 2003 Dec 15;198(12):1875-86
references.pmid: 14676299
references.citation: Proc Natl Acad Sci U S A. 1996 Sep 3;93(18):9821-6
references.pmid: 8790415
references.citation: Am J Transl Res. 2012;4(2):219-28
references.pmid: 22611474
references.citation: Allergy. 2011 Aug;66(8):1038-46
references.pmid: 21426359
references.citation: J Immunol. 2006 Sep 15;177(6):3534-41
references.pmid: 16951312
references.citation: Cell Biosci. 2011 May 24;1(1):20
references.pmid: 21711933
references.citation: Mol Cell Biochem. 2011 Jan;346(1-2):49-56
references.pmid: 20878350
references.citation: PLoS One. 2011;6(11):e27501
references.pmid: 22087328
references.citation: Genomics. 1990 May;7(1):123-6
references.pmid: 2335352
references.citation: Immunity. 2009 Sep 18;31(3):438-49
references.pmid: 19766086
references.citation: Nat Rev Immunol. 2012 Jun;12(6):417-30
references.pmid: 22627860
references.citation: Hepatology. 2012 May;55(5):1562-73
references.pmid: 22105716
references.citation: Allergy. 2013 Oct;68(10):1241-8
references.pmid: 24033604
references.citation: Immunotherapy. 2011 Apr;3(4 Suppl):19-20
references.pmid: 21524162
references.citation: N Engl J Med. 2000 May 4;342(18):1350-8
references.pmid: 10793168
references.citation: J Immunol. 2002 Oct 15;169(8):4183-9
references.pmid: 12370347
references.citation: Front Immunol. 2012 Jul 03;3:183
references.pmid: 22783257
references.citation: J Immunol. 2011 May 15;186(10):5569-79
references.pmid: 21464089
references.citation: Crit Rev Oncol Hematol. 2004 Mar;49(3):245-58
references.pmid: 15036264
references.citation: Nat Rev Immunol. 2010 Jul;10(7):490-500
references.pmid: 20559327
references.citation: PLoS One. 2012;7(9):e44338
references.pmid: 22962611
references.citation: Cell Immunol. 2013 May-Jun;283(1-2):75-80
references.pmid: 23887049
references.citation: J Thromb Haemost. 2012 Apr;10(4):647-61
references.pmid: 22268819
references.citation: Eur J Immunol. 2004 Nov;34(11):3082-90
references.pmid: 15376190
references.citation: Curr Opin Gastroenterol. 2012 Mar;28(2):99-103
references.pmid: 22134223
references.citation: Sci Rep. 2013;3:3345
references.pmid: 24736213
references.citation: J Leukoc Biol. 2011 Oct;90(4):751-9
references.pmid: 21724807
references.citation: J Allergy Clin Immunol. 2012 Jun;129(6):1579-1587.e1
references.pmid: 22554705