SLAP negatively regulates FcɛRI receptor-mediated mast cell response in mice

• Published in: The Journal of immunology (1950) 2016-05, Vol.196 (1_Supplement), p.203-203.23
• Main Authors: Sharma, Namit, Ernoult, Emilie, McGlade, Catherine Jane
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.196.Supp.203.23

Mast cells (MCs) are key mediators of innate immune response to pathogens and allergens, etiological factors for drugs, dust and peanut-induced anaphylaxis. Degranulation of MCs in response to binding of high affinity FcɛRI receptor (IgE receptor) to allergen-induced IgE results in the release of preformed mediators including histamine, and de novo synthesis of cytokines causing hypersensitivity symptoms including anaphylaxis. Src-like adapter protein (SLAP), has been shown to regulate signaling downstream of T cell receptor (TCR), B cell receptor (BCR) and receptor tyrosine kinases (RTK) including c-Kit, FLT3 and CSF-1 via recruitment of the Cbl ubiquitin ligase. Here, we show that bone marrow-derived mast cells (BMMCs) from SLAP knockout (SLAP KO) mice displayed significantly enhanced degranulation and de novo synthesis of IL-6 but not TNFα compared to wild type (WT) BMMCs. SLAP KO BMMCs also displayed significantly reduced F-actin polymerization upon stimulation of IgE receptor in comparison to WT BMMCs. In addition, SLAP KO BMMCs maintained enhanced cell surface expression of FcɛRI receptor post stimulation suggesting reduced endocytosis/degradation. While WT and SLAP KO mice have equal numbers of MCs in ear skin, SLAP KO mice showed enhanced passive cutaneous anaphylaxis response. Thus, these results suggest that SLAP negatively regulates MC-induced anaphylaxis reaction via IgE-DNP pathway.