Mast cells are critical in the pathogenesis of allergic disease due to the release of preformed and newly synthesized mediators, but the mechanisms controlling mast cell activation are not well understood. The tetraspanin family has recently emerged as novel signaling molecules and negative regulators of “outside-in” signals for mast cell activation. Specifically, antibodies against tetraspanins CD63 or CD81 can inhibit FcϵRI-mediated mast cells degranulation. CD151, a poorly understood member of this famility, is specifically induced in human mast cells upon FcϵRI aggregation, however, the functional significance of this response is not yet known. In this study, we found that CD151 deficiency significantly exacerbated the IgE-mediated late phase inflammation in a murine model of passive cutaneous anaphylaxis. Bone marrow-derived mast cells from CD151-deficient mice exhibited significantly enhanced de novo synthesis of pro-inflammatory cytokines IL-3, IL-4, IL-13 and TNF-α compared to controls. However, FcϵRI-induced mast cell degranulation from these mice was unaffected. At the molecular signaling level, CD151 appeared to selectively regulate IgE-induced activation of Syk and ERK1/2 associated with cytokine production but had no effect on the PLCγ1 pathway associated with degranulation. Collectively, our data indicate that tetraspanin CD151 exerts a selective negative regulation over IgE-induced late phase anaphylactic reaction and cytokine production in mast cells.
- Copyright © 2013 by The American Association of Immunologists, Inc.