title: The inhibitory effects of intravenous administration of rabbit immunoglobulin G on airway inflammation are dependent upon Fcγ receptor IIb on CD11c(+) dendritic cells in a murine model.
abstract: Immunoglobulins (Igs) play important immunomodulatory effects on allergic asthma. Among these, IgG has been reported to regulate allergic inflammation in previous studies about immunotherapy and intravenous immunoglobulin therapy. In this study, to examine the immunomodulatory mechanisms of IgG and FcRs we evaluated the effects of intravenous (i.v.) rabbit IgG administration (IVIgG) on allergic airway inflammation and lung antigen-presenting cells (APCs) in a murine model of ovalbumin (OVA) sensitization and challenge. In OVA-challenged mice, IVIgG attenuated airway eosinophilia, airway hyperresponsiveness and goblet cell hyperplasia and also inhibited the local T helper type (Th) 2 cytokine levels. Additionally, IVIgG attenuated the proliferation of OVA-specific CD4(+) T cells transplanted into OVA-challenged mice. Ex vivo co-culture with OVA-specific CD4(+) cells and lung CD11c(+) APCs from mice with IVIgG revealed the attenuated transcription level of Th2 cytokines, suggesting an inhibitory effect of IVIgG on CD11c(+) APCs to induce Th2 response. Next, to analyse the effects on Fcγ receptor IIb and dendritic cells (DCs), asthmatic features in Fcγ receptor IIb-deficient mice were analysed. IVIgG failed to attenuate airway eosinophilia, airway inflammation and goblet cell hyperplasia. However, the lacking effects of IVIgG on airway eosinophilia in Fcγ receptor IIb deficiency were restored by i.v. transplantation of wild-type bone marrow-derived CD11c(+) DCs. These results demonstrate that IVIgG attenuates asthmatic features and the function of lung CD11c(+) DCs via Fcγ receptor IIb in allergic airway inflammation. Targeting Fc portions of IgG and Fcγ receptor IIb on CD11c(+) DCs in allergic asthma is a promising therapeutic strategy.
authors.affiliation: Department of Internal Medicine, Kobe University Graduate School of Medicine, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Yamamoto
authors.forename: K
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: K
authors.initials: K
authors.lastname: Nakata
authors.forename: Y
authors.initials: Y
authors.lastname: Funada
authors.forename: Y
authors.initials: Y
authors.lastname: Kotani
authors.forename: A
authors.initials: A
authors.lastname: Masuda
authors.forename: T
authors.initials: T
authors.lastname: Takai
authors.forename: T
authors.initials: T
authors.lastname: Azuma
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Nishimura
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology; D001249:Asthma / Q000276:immunology / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D016535:Bronchial Hyperreactivity / Q000503:physiopathology / Q000517:prevention & control; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D039521:CD11c Antigen / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000637:transplantation; D004195:Disease Models, Animal; D004804:Eosinophils / Q000166:cytology; D005260:Female; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000494:pharmacology* / Q000627:therapeutic use; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology* / Q000627:therapeutic use; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D017452:Receptors, IgG / Q000235:genetics*; D013047:Specific Pathogen-Free Organisms; D018418:Th2 Cells / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; C499172:Fcgr2b protein, mouse; D007074:Immunoglobulin G; D016756:Immunoglobulins, Intravenous; D007155:Immunologic Factors; D017452:Receptors, IgG; D007073:Immunoglobulin E; D010047:Ovalbumin
references.citation: Am J Respir Crit Care Med. 1997 Sep;156(3 Pt 1):766-75
references.pmid: 9309991
references.citation: J Exp Med. 1999 Jan 18;189(2):371-80
references.pmid: 9892619
references.citation: Am J Respir Crit Care Med. 2004 Sep 15;170(6):583-93
references.pmid: 15172898
references.citation: PLoS One. 2010 Feb 22;5(2):e9337
references.pmid: 20179765
references.citation: J Immunol. 2007 Jan 1;178(1):480-8
references.pmid: 17182587
references.citation: Nature. 1996 Jan 25;379(6563):346-9
references.pmid: 8552190
references.citation: Annu Rev Immunol. 1999;17:255-81
references.pmid: 10358759
references.citation: Clin Exp Allergy. 2008 Feb;38(2):313-9
references.pmid: 18070161
references.citation: Clin Exp Allergy. 2007 Sep;37(9):1392-403
references.pmid: 17845421
references.citation: J Allergy Clin Immunol. 2003 Dec;112(6):1147-54
references.pmid: 14657874
references.citation: J Allergy Clin Immunol. 1999 May;103(5 Pt 1):810-5
references.pmid: 10329814
references.citation: Cytometry A. 2004 Oct;61(2):170-77
references.pmid: 15382026
references.citation: Am J Respir Cell Mol Biol. 1999 Mar;20(3):379-87
references.pmid: 10030835
references.citation: J Exp Med. 2007 Jan 22;204(1):11-5
references.pmid: 17227911
references.citation: J Clin Invest. 2005 Dec;115(12):3440-50
references.pmid: 16284651
references.citation: J Exp Med. 1992 Dec 1;176(6):1693-702
references.pmid: 1460426
references.citation: Nat Rev Immunol. 2002 Aug;2(8):580-92
references.pmid: 12154377
references.citation: Curr Opin Immunol. 2004 Dec;16(6):702-8
references.pmid: 15511661
references.citation: Infect Immun. 2001 Feb;69(2):1127-33
references.pmid: 11160010
references.citation: Clin Immunol. 1999 May;91(2):126-33
references.pmid: 10227804
references.citation: J Immunol. 2003 Aug 15;171(4):2080-9
references.pmid: 12902514
references.citation: J Exp Med. 2005 Mar 21;201(6):981-91
references.pmid: 15781587
references.citation: Chest. 1998 Nov;114(5):1349-56
references.pmid: 9824013
references.citation: J Allergy Clin Immunol. 1998 Jun;101(6 Pt 1):747-54
references.pmid: 9648701
references.citation: Clin Exp Allergy. 2005 Sep;35(9):1125-34
references.pmid: 16164437
references.citation: Intern Med J. 2003 Aug;33(8):341-4
references.pmid: 12895163
references.citation: Science. 2001 Jan 19;291(5503):484-6
references.pmid: 11161202
references.citation: J Immunol. 2007 May 15;178(10):6217-26
references.pmid: 17475849
references.citation: Immunity. 2006 Jan;24(1):19-28
references.pmid: 16413920
references.citation: J Exp Med. 2002 Jun 17;195(12):1653-9
references.pmid: 12070293
references.citation: J Exp Med. 1997 Mar 3;185(5):885-92
references.pmid: 9120394