First Author | Habener A | Year | 2021 |
Journal | J Allergy Clin Immunol | Volume | 147 |
Issue | 6 | Pages | 2281-2294.e7 |
PubMed ID | 33249168 | Mgi Jnum | J:336622 |
Mgi Id | MGI:6822197 | Doi | 10.1016/j.jaci.2020.09.041 |
Citation | Habener A, et al. (2021) Regulatory B cells control airway hyperreactivity and lung remodeling in a murine asthma model. J Allergy Clin Immunol 147(6):2281-2294.e7 |
abstractText | BACKGROUND: Asthma is a widespread, multifactorial chronic airway disease. The influence of regulatory B cells on airway hyperreactivity (AHR) and remodeling in asthma is poorly understood. OBJECTIVE: Our aim was to analyze the role of B cells in a house dust mite (HDM)-based murine asthma model. METHODS: The influence of B cells on lung function, tissue remodeling, and the immune response were analyzed by using wild-type and B-cell-deficient (muMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to muMT mice. RESULTS: After HDM-sensitization, both wild-type and muMT mice developed AHR, but the AHR was significantly stronger in muMT mice, as confirmed by 2 independent techniques: invasive lung function measurement in vivo and examination of precision-cut lung slices ex vivo. Moreover, airway remodeling was significantly increased in allergic muMT mice, as shown by enhanced collagen deposition in the airways, whereas the numbers of FoxP3(+) and FoxP3(-) IL-10-secreting regulatory T cells were reduced. Adoptive transfer of IL-10-proficient but not IL-10-deficient B cells into muMT mice before HDM-sensitization attenuated AHR and lung remodeling. In contrast, FoxP3(+) regulatory T cells were equally upregulated by transfer of IL-10-proficient and IL-10-deficient B cells. CONCLUSION: Our data in a murine asthma model illustrate a central role of regulatory B cells 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. |