Science and Research

Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model

BACKGROUND: Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells (Bregs) on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood. OBJECTIVE: We analyzed the role of B cells in a house dust mite (HDM)-based murine asthma model. METHODS: By employing wildtype (WT) and B cell-deficient (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice, the influence of B cells on lung function, tissue remodeling and the immune response was analyzed. RESULTS: After HDM-sensitization, both WT and μMT mice developed AHR, but AHR was significantly stronger in μMT mice as confirmed by two independent techniques: invasive lung function measurement in vivo and precision-cut lung slices ex vivo. Moreover, airway remodeling was significantly increased in allergic μMT mice as shown by enhanced collagen deposition in the airways, while regulatory FoxP3(+) and FoxP3(-) IL-10-secreting T cells (Tregs) were reduced. Adoptive transfer of IL-10-proficient, but not IL-10-deficient B cells into μMT mice prior to HDM-sensitization, attenuated AHR and lung remodeling. In contrast, FoxP3(+) Tregs were equally upregulated by transfer of IL-10-proficient as well as IL-10-deficient B cells. CONCLUSION: Our data in a murine asthma model illustrate a central role of Bregs in the control of lung function and airway remodeling, and may support future concepts for B cell targeted prevention and treatment strategies for allergic asthma.

  • Dipl-Biol, A. H.
  • Happle, C.
  • Grychtol, R. M.
  • Skuljec, J.
  • Busse, M.
  • Dalüge, K.
  • Obernolte, H.
  • Sewald, K.
  • Braun, A.
  • Meyer-Bahlburg, A.
  • Hansen, G.

Keywords

  • B cell transfer
  • Il-10
  • airway hyperreactivity
  • allergy
  • experimental asthma
  • house dust mite
  • lung remodeling
  • precision-cut lung slices
  • regulatory B cells
Publication details
DOI: 10.1016/j.jaci.2020.09.041
Journal: J Allergy Clin Immunol
Work Type: Original
Location: BREATH
Disease Area: AA
Partner / Member: ITEM, MHH
Access-Number: 33249168

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