A schematic model of the pathogenesis of CSU. The extrinsic coagulation pathway is activated by tissue factors derived from eosinophils and monocytes, which contributes to the degranulation of mast cells and basophils. Autoimmunity, infections, stress, intestinal dysbiosis, and Vitamin D deficiency also lead to mast cell degranulation via different molecular pathways. TSLP combined with IL-25 and IL-33 are suggested to be activating factors of ILC2s, which release IL-5 and IL-13 to promote mast cell degranulation. T cells and eosinophils perform complex bidirectional crosstalk with mast cells. Besides, macrophages and NK cells may also play a role in CSU pathogenesis. C5a, complement 5a; FXa, activated factor X; TF, tissue factor; FceRI, high-affinity IgE receptor; Syk, spleen tyrosine kinase; SHIP, Src homology 2-containing inositol 5’ phosphatase; PGD2, prostaglandin D2; LTC4, Leukotriene C4; MMP-9, matrix metalloproteinase-9; TSLP, thymic stromal lymphopoietin; MCP-1, monocyte chemoattractant protein 1; ECP, eosinophil cationic protein; EPO, eosinophil peroxidase; MBP, major basic protein; SCF, stem cell factor.