Development of eosinophilic inflammation is independent of B-T cell interaction in a chronic house dust mite-driven asthma model

Clin Exp Allergy. 2017 Apr;47(4):551-564. doi: 10.1111/cea.12834. Epub 2016 Nov 22.

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.

Aims: 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.

Conclusion and clinical relevance: 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.

Keywords: B cells; Tfh cells; Th2 cells; asthma; house dust mite.

MeSH terms

  • Airway Remodeling
  • Allergens / immunology*
  • Animals
  • Asthma / immunology*
  • Asthma / metabolism
  • Asthma / pathology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • Biomarkers
  • CD40 Ligand / metabolism
  • Cell Communication / immunology*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Eosinophils / pathology*
  • Female
  • Inflammation Mediators / metabolism
  • Leukocyte Count
  • Male
  • Mice
  • Mice, Knockout
  • Pyroglyphidae / immunology*
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism

Substances

  • Allergens
  • Biomarkers
  • Cytokines
  • Inflammation Mediators
  • CD40 Ligand