炎症致特应性皮炎皮肤屏障功能破坏的机制和干预策略

IL-31是致特应性皮炎（AD）瘙痒及皮肤屏障功能破坏的重要炎症因子。金葡菌外毒素（SE）可诱导CLA+T细胞分泌IL-31，本课题组发现SE下调抗菌肽（AMP），而AMP与肥大细胞分泌IL-31正相关，那么SE对IL-31的最终作用是上调还是下调？靶向治疗下调皮损中CLA+T细胞数量可改善AD，但致外周血CLA+T细胞增多，那么外周血IL-31是否上调，从而增加AD复发风险？本课题组发现利多卡因促进Treg分化并上调FLG表达，但机制仍待深入研究。本研究拟①探究SE刺激下CLA+T细胞和肥大细胞分泌IL-31水平，揭示血液及皮损CLA+T细胞数量和IL-31水平与疾病的相关性；②明确利多卡因是直接抑制KCs表面MHCII高表达或间接抑制上游IL-31释放，从而上调FLG表达；③探索利多卡因干预前后KCs中Na+内流及IL-31RA-TRPV1中Ca2+内流的差异，明确其对瘙痒影响的机制。

IL-31 was an important inflammatory factor in atopic dermatitis(AD), which led to pruritus and disrupted skin barrier function. The effect of Staphylococcal Enterotoxin（SE）on IL-31 was paradoxical: it stimulated CLA+T cells to produce much IL-31 in vitro while it also down-regulated antimicrobial peptide(AMP) in keratinocytes(KCs), which paralleled to mast cell-dependent IL-31 expression. CLA+ T cells targeted therapy improved AD by reducing CLA+ T cells in lesional skin, but CLA+ T cells in peripheral blood increased. Then the expression of IL-31 remained unknown and the up-regulation of IL-31 might be a risk factor of AD relapse. Our previous research verified that lidocaine could promote the differentiation of regulatory T cells and up-regulate FLG expression, but the mechanism should be a further research. So our aims of the research are as follows: ①We aim to clarify the relationship between the production of IL-31 in SE-stimulated CLA+T cells and that in mast cells. The association between CLA+ T cells, which are both in blood and lesional skin, and the expression of IL-31 will also be detected.②We plan to verify if lidocaine up-regulates FLG expression via inhibiting the expression of MHCII on KCs or reducing the upstream production of IL-31. ③We intend to explore the role of lidocaine in Na+ influx or IL-31RA-TRPV1 mediated Ca2+ influx in KCs , which uncovers the mechanism of its regulation of pruritus .