Glycogen synthase kinase 3 (GSK3) is a critical regulator of allergen-mediated mast cell activation

• Published in: The Journal of immunology (1950) 2021-05, Vol.206 (1_Supplement), p.23-23.09
• Main Authors: Crozier, Robert W.E., Hamstra, Sophie I., Fajardo, Val A., MacNeil, Adam J.
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.206.Supp.23.09

Mast cells are granulated immune sentinels responsible for perpetuating allergic inflammatory events. Allergen-induced FcɛRI signaling leads to the activation of MAPK, PLC and PI3K/Akt signaling cascades, which are responsible for mediating a biphasic mast cell response, characterized by degranulation in the early phase and sustained release of pro-inflammatory mediators in the late phase. Glycogen synthase kinase 3 (GSK3) is a constitutively active serine/threonine kinase and a major convergence point for several highly conserved signaling cascades, including the PI3K/Akt pathway. Due to its central role in regulating downstream pro-inflammatory signals, GSK3 has become a therapeutic target in inflammatory pathologies, however, the role that GSK3 plays in allergen-induced FcɛRI signaling has yet to be characterized. Thus, the objective of this study was to determine the functional role of GSK3 in allergen-activated mast cells. Sensitized murine bone marrow-derived mast cells were incubated with the GSK3 inhibitor CHIR99021 and stimulated with allergen. CHIR99021 treatment significantly inhibited degranulation dose-dependently to 63% (10 μM, p