title: T Follicular Helper Cell Plasticity Shapes Pathogenic T Helper 2 Cell-Mediated Immunity to Inhaled House Dust Mite.
abstract: Exposure to environmental antigens, such as house dust mite (HDM), often leads to T helper 2 (Th2) cell-driven allergic responses. However, the mechanisms underlying the development of these responses are incompletely understood. We found that the initial exposure to HDM did not lead to Th2 cell development but instead promoted the formation of interleukin-4 (IL-4)-committed T follicular helper (Tfh) cells. Following challenge exposure to HDM, Tfh cells differentiated into IL-4 and IL-13 double-producing Th2 cells that accumulated in the lung and recruited eosinophils. B cells were required to expand IL-4-committed Tfh cells during the sensitization phase, but did not directly contribute to disease. Impairment of Tfh cell responses during the sensitization phase or Tfh cell depletion prevented Th2 cell-mediated responses following challenge. Thus, our data demonstrate that Tfh cells are precursors of HDM-specific Th2 cells and reveal an unexpected role of B cells and Tfh cells in the pathogenesis of allergic asthma.
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: André
authors.initials: A
authors.lastname: Ballesteros-Tato
authors.affiliation: Department of Medicine, Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Troy D
authors.initials: TD
authors.lastname: Randall
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lund
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung and Blood institute, Bethesda, MD 20892, USA.
authors.forename: Rosanne
authors.initials: R
authors.lastname: Spolski
authors.affiliation: Laboratory of Molecular Immunology, National Heart, Lung and Blood institute, Bethesda, MD 20892, USA.
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Leonard
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA. Electronic address: bleon@uab.edu.
authors.forename: Beatriz
authors.initials: B
authors.lastname: León
mesh_terms: D000818:Animals; D039741:Antigens, Dermatophagoides / Q000008:administration & dosage / Q000276:immunology; D001249:Asthma / Q000209:etiology / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology*; D007109:Immunity; D001239:Inhalation; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008212:Lymphocyte Depletion; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D039981:Pyroglyphidae; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D039741:Antigens, Dermatophagoides; D018793:Interleukin-13; D015847:Interleukin-4
references.citation: Immunity. 2012 May 25;36(5):847-56
references.pmid: 22464171
references.citation: Nat Immunol. 2012 May;13(5):491-8
references.pmid: 22466669
references.citation: Immunity. 2013 Feb 21;38(2):322-35
references.pmid: 23352232
references.citation: Immunity. 2013 Mar 21;38(3):596-605
references.pmid: 23499493
references.citation: J Immunol. 2013 Apr 15;190(8):4014-26
references.pmid: 23487426
references.citation: Immunol Cell Biol. 2014 Jan;92(1):22-7
references.pmid: 24145854
references.citation: Eur J Immunol. 2013 Dec;43(12):3125-37
references.pmid: 24165907
references.citation: Curr Opin Immunol. 2013 Dec;25(6):745-54
references.pmid: 24455765
references.citation: Immunity. 2014 Mar 20;40(3):425-35
references.pmid: 24613091
references.citation: J Immunol. 2014 Aug 15;193(4):1531-7
references.pmid: 25086176
references.citation: Immunity. 2014 Oct 16;41(4):529-42
references.pmid: 25367570
references.citation: Immunity. 2015 Aug 18;43(2):318-30
references.pmid: 26287681
references.citation: J Exp Med. 2000 Jan 17;191(2):201-6
references.pmid: 10637265
references.citation: Immunity. 2001 Aug;15(2):303-11
references.pmid: 11520464
references.citation: J Immunol. 2004 Jul 15;173(2):1298-306
references.pmid: 15240723
references.citation: Nature. 2008 Jul 24;454(7203):445-54
references.pmid: 18650915
references.citation: PLoS One. 2008;3(9):e3129
references.pmid: 18769622
references.citation: Nat Immunol. 2008 Nov;9(11):1288-96
references.pmid: 18820682
references.citation: J Exp Med. 2009 May 11;206(5):1001-7
references.pmid: 19380638
references.citation: Annu Rev Physiol. 2009;71:489-507
references.pmid: 19575684
references.citation: Cancer Cell. 2010 Apr 13;17(4):400-11
references.pmid: 20385364
references.citation: Immunity. 2010 Aug 27;33(2):241-53
references.pmid: 20691615
references.citation: J Exp Med. 2010 Sep 27;207(10):2097-111
references.pmid: 20819925
references.citation: Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9542-7
references.pmid: 21593413
references.citation: Immunity. 2011 Jun 24;34(6):947-60
references.pmid: 21636295
references.citation: Immunity. 2011 Jun 24;34(6):932-46
references.pmid: 21636296
references.citation: J Immunol. 2011 Aug 1;187(3):1091-5
references.pmid: 21715693
references.citation: Immunity. 2011 Oct 28;35(4):622-32
references.pmid: 22018472
references.citation: Nat Immunol. 2012 Jan;13(1):58-66
references.pmid: 22138715
references.citation: Nat Immunol. 2012 Jul;13(7):681-90
references.pmid: 22634865