B cell depletion increases sphingosine-1-phosphate-dependent airway inflammation in mice

Rosalinda Sorrentino, Antonio Bertolino, Michela Terlizzi, Valentina Mattera Iacono, Piera Maiolino, Giuseppe Cirino, Fiorentina Roviezzo, Aldo Pinto

Research output: Contribution to journalArticlepeer-review

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 S1 P-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.

Original languageEnglish
Pages (from-to)571-583
Number of pages13
JournalAmerican Journal of Respiratory Cell and Molecular Biology
Volume52
Issue number5
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Asthma
  • B cells
  • Immunosuppression
  • Lung inflammation
  • Sphingosine-1-phosphate

ASJC Scopus subject areas

  • Cell Biology
  • Pulmonary and Respiratory Medicine
  • Molecular Biology
  • Clinical Biochemistry
  • Medicine(all)

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