title: A regulatory CD9(+) B-cell subset inhibits HDM-induced allergic airway inflammation.
abstract: BACKGROUND
  Exposure to respiratory allergens triggers airway hyperresponsiveness and inflammation characterized by the expansion of TH 2 cells and the production of allergen specific IgE. Allergic asthma is characterized by an alteration in immune regulatory mechanisms leading to an imbalance between pro- and anti-inflammatory components of the immune system.
  
  
  OBJECTIVE
  Recently B cells have been described as central regulators of exacerbated inflammation, notably in the case of autoimmunity. However, to what extent these cells can regulate airway inflammation and asthma remains to be elucidated.
  
  
  METHODS
  We took advantage of a allergic asthma model in mice induced by percutaneous sensitization and respiratory challenge with an extract of house dust mite.
  
  
  RESULTS
  In this study, we showed that the induction of allergic asthma alters the homeostasis of IL-10(+) Bregs and favors the production of inflammatory cytokines by B cells. Deeper transcriptomic and phenotypic analysis of Bregs revealed that they were enriched in a CD9(+) B cell subset. In asthmatic mice the adoptive transfer of CD9(+) B cells normalized airway inflammation and lung function by inhibiting TH 2- and TH 17-driven inflammation in an IL-10-dependent manner, restoring a favorable immunological balance in lung tissues. Indeed we further showed that injection of CD9(+) Bregs controls the expansion of lung effector T cells allowing the establishment of a favorable regulatory T cells/effector T cells ratio in lungs.
  
  
  CONCLUSIONS
  This finding strengthens the potential for Breg-targeted therapies in allergic asthma.
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.|INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|CIC biothérapie, Nantes, France.|Université de Nantes, Nantes, France.
authors.forename: F
authors.identifier: http://orcid.org/0000-0003-1182-1413
authors.initials: F
authors.lastname: Braza
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.|INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|CIC biothérapie, Nantes, France.|Université de Nantes, Nantes, France.
authors.forename: J
authors.initials: J
authors.lastname: Chesne
authors.affiliation: INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|CIC biothérapie, Nantes, France.|Université de Nantes, Nantes, France.
authors.forename: M
authors.initials: M
authors.lastname: Durand
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.|CHU Nantes, l'institut du thorax, Service de Pneumologie, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Dirou
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.|INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|CHU Nantes, l'institut du thorax, Service de Pneumologie, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Brosseau
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.
authors.forename: G
authors.initials: G
authors.lastname: Mahay
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.
authors.forename: M A
authors.initials: MA
authors.lastname: Cheminant
authors.affiliation: INSERM, UMR 1087, l'institut du thorax, Nantes, France.|CNRS, UMR 6291, Nantes, France.|Université de Nantes, Nantes, France.|CHU Nantes, l'institut du thorax, Service de Pneumologie, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Magnan
authors.affiliation: INSERM, UMR 1064, Nantes, France.|CHU de Nantes, ITUN, Nantes, France.|CIC biothérapie, Nantes, France.|Université de Nantes, Nantes, France.
authors.forename: S
authors.initials: S
authors.lastname: Brouard
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000276:immunology; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000276:immunology; D016753:Interleukin-10 / Q000172:deficiency / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D012130:Respiratory Hypersensitivity / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D060245:Tetraspanin 29 / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D059467:Transcriptome
chemical_list: D000485:Allergens; D000954:Antigens, Surface; D015415:Biomarkers; D016207:Cytokines; D060245:Tetraspanin 29; D016753:Interleukin-10; D007073:Immunoglobulin E
keywords: IL-10; airway inflammation; allergic asthma; regulatory B cells