Tetraspanin CD151 is a negative regulator of FcεRI-mediated mast cell activation

Hiam Abdala-Valencia, Paul J. Bryce, Robert P. Schleimer, Joshua B. Wechsler, Lucas F. Loffredo, Joan M. Cook-Mills, Chia Lin Hsu, Sergejs Berdnikovs*

*Corresponding author for this work

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, yet the mechanisms controlling mast cell activation are not well understood. Members of the tetraspanin family are recently emerging as modulators of FcεRI-mediated mast cell activation; however, mechanistic understanding of their function is currently lacking. The tetraspanin CD151 is a poorly understood member of this family and is specifically induced on mouse and human mast cells upon FcεRI aggregation but its functional effects are unknown. In this study, we show that CD151 deficiency significantly exacerbates the IgEmediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Ex vivo, FcεRI stimulation of bone marrow- derived mast cells from CD151-/- mice resulted in significantly enhanced expression of proinflammatory cytokines IL-4, IL-13, and TNF-A compared with wild-type controls. However, FcεRI-induced mast cell degranulation was unaffected. At the molecular signaling level, CD151 selectively regulated IgE-induced activation of ERK1/2 and PI3K, associated with cytokine production, but had no effect on the phospholipase Cg1 signaling, associated with degranulation. Collectively, our data indicate that CD151 exerts negative regulation over IgE-induced late phase responses and cytokine production in mast cells.

Original languageEnglish (US)
Pages (from-to)1377-1387
Number of pages11
JournalJournal of Immunology
Volume195
Issue number4
DOIs
StatePublished - Aug 15 2015

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint Dive into the research topics of 'Tetraspanin CD151 is a negative regulator of FcεRI-mediated mast cell activation'. Together they form a unique fingerprint.

  • Cite this