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IL-4 and IL-13 promote the differentiation of nave CD4+ T helper cells (Th0) into T helper 2 cells (Th2) cells and maintain their effector function ( 2.4 Crosstalk with the neurovascular system A bidirectional regulatory relationship exists between the mast cellneuron axis and the local cutaneous vasculature, forming a key conduit for inflammatory spread and peripheral neural sensitization ( Upon activation, MCs rapidly release a repertoire of vasoactive mediators, including histamine, ATP, prostaglandin D 2 (PGD 2 ), leukotrienes (e.g., LTC 4 ), vascular endothelial growth factor (VEGF), and TNF- (50, 51).Conversely, sensory neurons, upon activation, release neuropeptides such as SP and CGRP, which act directly on vascular smooth muscle cells and endothelial cells to induce neurogenic vasodilation and plasma extravasation (52, 53)

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