title: B cell depletion increases sphingosine-1-phosphate-dependent airway inflammation in mice.
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.
authors.affiliation: 1 Department of Pharmacy, University of Salerno, Fisciano, Italy.
authors.forename: Rosalinda
authors.initials: R
authors.lastname: Sorrentino
authors.forename: Antonio
authors.initials: A
authors.lastname: Bertolino
authors.forename: Michela
authors.initials: M
authors.lastname: Terlizzi
authors.forename: Valentina Mattera
authors.initials: VM
authors.lastname: Iacono
authors.forename: Piera
authors.initials: P
authors.lastname: Maiolino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cirino
authors.forename: Fiorentina
authors.initials: F
authors.lastname: Roviezzo
authors.forename: Aldo
authors.initials: A
authors.lastname: Pinto
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D018951:Antigens, CD20 / Q000276:immunology / Q000378:metabolism; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016535:Bronchial Hyperreactivity / Q000139:chemically induced / Q000276:immunology / Q000503:physiopathology; D016084:Bronchoconstriction; D049109:Cell Proliferation; D002634:Chemotaxis, Leukocyte; D004195:Disease Models, Animal; D005260:Female; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D018793:Interleukin-13 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008213:Lymphocyte Activation; D008246:Lysophospholipids; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism; D011014:Pneumonia / Q000139:chemically induced* / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism; D000099157:Sphingosine Kinase
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D018836:Inflammation Mediators; D016753:Interleukin-10; D018793:Interleukin-13; D008246:Lysophospholipids; D010047:Ovalbumin; D017853:Phosphotransferases (Alcohol Group Acceptor); D047428:Protein Kinase Inhibitors; D013110:Sphingosine; D016212:Transforming Growth Factor beta; D000099157:Sphingosine Kinase; C508609:IL10 protein, human; C060506:sphingosine 1-phosphate
keywords: B cells; asthma; immunosuppression; lung inflammation; sphingosine-1-phosphate