Anika Habener1, Christine Happle1, Ruth Grychtol1, Jelena Skuljec2, Mandy Busse3, Kathleen Dalüge4, Helena Obernolte5, Katherina Sewald5, Armin Braun5, Almut Meyer-Bahlburg6, Gesine Hansen7. 1. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany. 2. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Department of Neurology, University Medicine Essen, Essen, Germany. 3. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Experimental Obstetrics and Gynecology, Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. 4. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany. 5. Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany; Fraunhofer Institute for Toxicology and Experimental Medicine, Hannover, Germany. 6. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany; Department of Pediatrics, University Medicine Greifswald, Greifswald, Germany. 7. Department of Paediatric Pneumology, Allergology and Neonatology, Hannover Medical School, Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research, Hannover, Germany; Cluster of Excellence RESIST (EXC 2155), Hannover Medical School, Hannover, Germany. Electronic address: hansen.gesine@mh-hannover.de.
Abstract
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 (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice. RESULTS: After HDM-sensitization, both wild-type and μMT mice developed AHR, but the AHR was significantly stronger in μMT 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 μMT 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 μMT 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.
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 murineasthma 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 (μMT) mice and transfer of IL-10-proficient and IL-10-deficient B cells to μMT mice. RESULTS: After HDM-sensitization, both wild-type and μMT mice developed AHR, but the AHR was significantly stronger in μMT 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 μMT 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 μMT 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 murineasthma 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.
Authors: Diego Catalán; Miguel Andrés Mansilla; Ashley Ferrier; Lilian Soto; Kristine Oleinika; Juan Carlos Aguillón; Octavio Aravena Journal: Front Immunol Date: 2021-04-29 Impact factor: 7.561