1. B cell depletion increases sphingosine-1-phosphate-dependent airway inflammation in mice
- Author
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Aldo Pinto, Antonio Bertolino, Michela Terlizzi, Valentina Mattera Iacono, Piera Maiolino, Fiorentina Roviezzo, Rosalinda Sorrentino, Giuseppe Cirino, Sorrentino, Rosalinda, Bertolino, Antonio, Terlizzi, Michela, Iacono, Valentina Mattera, Maiolino, Piera, Cirino, Giuseppe, Roviezzo, Fiorentina, and Pinto, Aldo
- Subjects
Time Factors ,Clinical Biochemistry ,Lymphocyte Activation ,T-Lymphocytes, Regulatory ,chemistry.chemical_compound ,Sphingosine ,Transforming Growth Factor beta ,Inflammation Mediator ,Lung ,Lysophospholipid ,B cell ,B-Lymphocytes ,Mice, Inbred BALB C ,Interleukin-13 ,Kinase ,Medicine (all) ,B-Lymphocyte ,Antibodies, Monoclonal ,respiratory system ,Interleukin-10 ,Chemotaxis, Leukocyte ,Phosphotransferases (Alcohol Group Acceptor) ,medicine.anatomical_structure ,Female ,medicine.symptom ,Bronchial Hyperreactivity ,Inflammation Mediators ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Lung inflammation ,Time Factor ,Sphingosine-1-phosphate ,Ovalbumin ,T cell ,Bronchoconstriction ,Protein Kinase Inhibitor ,Inflammation ,Biology ,Internal medicine ,medicine ,Animals ,Asthma ,B cells ,Immunosuppression ,Molecular Biology ,Protein Kinase Inhibitors ,Cell Proliferation ,Animal ,Cell Biology ,Pneumonia ,Antigens, CD20 ,In vitro ,Disease Models, Animal ,Endocrinology ,chemistry ,Immunology ,biology.protein ,Lysophospholipids ,CD8 - Abstract
Sphingosine-1-phosphate (S1P) has been widely associated with inflammation-based lung pathologies. Because B cells play a critical role as antigen-presenting and/or Ig-producing cells during asthmatic conditions, we wanted to dissect the role of these cells in S1P-dependent airway hyperreactivity and inflammation. Mice were sensitized to ovalbumin or exposed to S1P. Ovalbumin sensitization caused airway hyperreactivity coupled to an increased lung infiltration of B cells, which was significantly reduced after the inhibition of sphingosine kinases I/II. Similarly, the sole administration of S1P increased bronchial reactivity compared with vehicle and was accompanied by a higher influx of B cells in a time-dependent manner. This effect was associated with higher levels of IL-13, transforming growth factor-β, IL-10, and T regulatory cells. In addition, isolated S1P-derived lung B cells increased CD4(+) and CD8(+) T cell proliferation in vitro, and their suppressive nature at Day 14 was associated with the higher release of transforming growth factor-β and IL-10 when they were cocultured. Therefore, to prove the role of B cells in S1P-mediated airway inflammation, and because CD20 expression, contrary to major hystocompatibility complex I and major hystocompatibility complex II, was up-regulated at Day 14, CD20(+) B cells were depleted by means of a specific monoclonal antibody. The absence of CD20(+) B cells increased airway reactivity and inflammation in S1P-treated mice compared with control mice. These data imply that sphingosine kinase/S1P-mediated airway inflammation is countered by B cells via the induction of an immune-suppressive environment to reduce asthma-like outcomes in mice.
- Published
- 2014