Study On The Effect And Mechanism Of Septin11 On Activation Of Mast Cells

Allergic diseases are a global health problem.Epidemiological surveys have shown that the incidence of allergic diseases is as high as 15-30%,which is listed by the World Health Organization as one of the three major diseases to be prevented in this century.The incidence of allergic diseases is high and the etiology is complex.The clinical manifestations are diverse and the diagnosis is confusing.It is still a difficult point in clinical diagnosis and treatment.In addition,there are few studies on the pathogenesis and therapeutic targets of allergic diseases.Mast cells are the last kind of immune cells involved in the process of allergic reactions,and are the most direct effector cells for allergic reactions.Studies have shown that Septin11 is involved in the activation of mast cells and can be enriched in the membrane of mast cells.However,it is unclear how Septin11 regulates the activation of mast cells.In this study,we used the P815 mast cell line as the research object,using the CRISPR/Cas9 gene editing technology to knock out Sept11?Septin11 protein?in P815 mast cells,and successfully constructed the P815-PX459-Septin11-KO stable cell line?KO cell for short?system).Knockdown of KO and WT mast cell activation with Compound 48/80 successfully established a mast cell activation model.Further in vitro experiments found that Septin11 promoted mast cell proliferation and migration,promoted mast cell activation and release of inflammatory factors.Studies have shown that Septin11 regulates mast cell activation through Ca²⁺—ERK signaling pathways,and the molecular mechanisms by which Septin11 regulates Ca2+-ERK signaling are unclear.At present,we propose a hypothesis:When C48/80 stimulates hypertrophy,Septin11 is enriched in the cell membrane and turns off calcium channels through certain molecular mechanisms,thereby inhibiting the influx of calcium ions.Influx of calcium is inhibited by activation of the downstream ERK signaling pathway,which in turn activates mast cell activation and promotes mast cell degranulation.