Technical advance: Soluble OX40 molecule mimics regulatory T cell modulatory activity on FcεRI-dependent mast cell degranulation

Riccardo Sibilano, Giorgia Gri, Barbara Frossi, Claudio Tripodo, Ryo Suzuki, Juan Rivera, Andrew S MacDonald, Carlo E Pucillo

Research output: Contribution to journalArticlepeer-review

Abstract

Tregs play a central role in modulating FcεRI-dependent MC effector functions in the course of the allergic response. Cellular interaction depends on the constitutive expression of OX40 on Tregs and the OX40L counterpart on MCs. Study of OX40L signaling on MCs is hampered by the need of a highly purified molecule, which triggers OX40L specifically. We now report that sOX40 mimics the physiological activity of Treg interaction by binding to activated MCs. When treated with sOX40, activated MCs showed decreased degranulation and Ca(++) influx, whereas PLC-γ2 phosphorylation remained unaffected. Once injected into experimental animals, sOX40 not only located within the endothelium but also in parenchyma, where it could be found in close proximity and apparently bound to MCs. This soluble molecule triggers MC-OX40L without the requirement of Tregs, thus allowing study of OX40L signaling pathways in MCs and in other OX40L-expressing cell populations. Importantly, as sOX40 inhibits MC degranulation, it may provide an in vivo therapeutic tool in allergic disease.
Original languageEnglish
Pages (from-to)831-838
Number of pages8
JournalJournal of Leukocyte Biology
Volume90
Issue number4
Early online date7 Jun 2011
DOIs
Publication statusPublished - 31 Oct 2011

Keywords

  • Animals
  • Cell Degranulation
  • Hypersensitivity
  • Mast Cells
  • Membrane Glycoproteins
  • Mice
  • Mice, Knockout
  • Phospholipase C gamma
  • Phosphorylation
  • Receptors, IgE
  • Receptors, OX40
  • Solubility
  • T-Lymphocytes, Regulatory
  • Tumor Necrosis Factors
  • cell activation
  • costimulation
  • allergy

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