Antigen-mediated cross-linking of IgE on mast cells triggers a signaling cascade that results in their degranulation and proinflammatory cytokine production, which are key effectors in allergic reactions. The research team led by Prof. Linrong Lu from Institute of Immunology, Medical school, Zhejiang University found that the activation of mast cells is negatively regulated by the newly identified adaptor protein Tespa1. Loss of Tespa1 in mouse mast cells led to hyper-responsiveness to stimulation via FcεRI. Mice lacking Tespa1 also displayed increased sensitivity to IgE-mediated allergic responses. The dysregulated signaling in KO mast cells was associated with increased activation of Grb2-PLC-γ1-SLP-76 signaling within the LAT1 (linker for activation of T cells family, member 1) signalosome versus the LAT2 signalosome. Collectively, these findings show that Tespa1 orchestrates mast cell activation by tuning the balance of LAT1 and LAT2 signalosome assembly. The related article “Tespa1 negatively regulates FcεRI-mediated signaling and the mast cell–mediated allergic response” was recently published on <Journal of Experimental Medicine> (IF=12.515). The first authors are Prof. Di Wang and Post doctoral Mingzhu Zheng, with Prof. Di Wang and Prof. Linrong Lu being the corresponding author.
