title: Development of eosinophilic inflammation is independent of B-T cell interaction in a chronic house dust mite-driven asthma model.
abstract: BACKGROUND
  Chronic exposure to environmental triggers, such as house dust mite (HDM), drives T helper 2 (Th2) cell-mediated asthma. Recent evidence has shown that B-T cell interaction, and in particular germinal centre reactions and follicular T helper (Tfh) cells are required for the development of eosinophilic airway inflammation in HDM-driven models containing a sensitization and challenge phase. Whether B-T cell interactions are essential for pulmonary eosinophilic inflammation following chronic allergen provocation remains unknown.
  
  
  OBJECTIVE
  In this study, we investigated the importance of B-T cell interaction in the development of eosinophilic airway inflammation and pulmonary remodelling in a chronic HDM-driven asthma model.
  
  
  METHODS
  We exposed C57BL/6, Cd40l-/-, and Mb1-/-mice to HDM three times a week for five consecutive weeks.
  
  
  RESULTS
  Chronic HDM exposure induced a pronounced eosinophilic allergic airway inflammation in broncho-alveolar lavage fluid (BALf) and lung tissue, associated with the formation of immunologically active inducible bronchus-associated lymphoid tissue (iBALT) in the lungs. The absence of B cells or lack of CD40L signalling did not hamper eosinophilic inflammation in the airways, although the number of Tfh and Th2 cells was substantially reduced in the lungs. Importantly, type 2 innate lymphoid cell (ILC2) numbers in BALf and lung were not affected by the absence of B cells or B-T cell interaction. Furthermore, eosinophilic airway inflammation is not sufficient to induce pulmonary remodelling and airway hyperresponsiveness.
  
  
  CONCLUSIONS
  From these findings, we conclude that B-T cell interaction is required for robust Tfh and Th2 cell induction, but not essential for eosinophilic airway inflammation during a chronic HDM-driven asthma model.
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: H
authors.initials: H
authors.lastname: Vroman
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: I M
authors.initials: IM
authors.lastname: Bergen
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: B W S
authors.initials: BW
authors.lastname: Li
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: J A C
authors.initials: JA
authors.lastname: van Hulst
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Lukkes
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: D
authors.initials: D
authors.lastname: van Uden
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: R W
authors.initials: RW
authors.lastname: Hendriks
authors.affiliation: Department of Pulmonary Medicine, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Kool
mesh_terms: D056151:Airway Remodeling; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D015415:Biomarkers; D023201:CD40 Ligand / Q000378:metabolism; D002450:Cell Communication / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004804:Eosinophils / Q000473:pathology*; D005260:Female; D018836:Inflammation Mediators / Q000378:metabolism; D007958:Leukocyte Count; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D039981:Pyroglyphidae / Q000276:immunology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism
chemical_list: D000485:Allergens; D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D023201:CD40 Ligand
keywords: B cells; Tfh cells; Th2 cells; asthma; house dust mite