Interleukin-31:A new link between T cells, pruitus and atopic skin inflammation

瘙痒是特应性皮肤炎症的主要症状，严重影响患者的生活质量。尽管最近在理解特应性皮肤炎症的免疫发病机制方面取得了进展，但瘙痒的潜在机制仍然知之甚少。最近有研究表明，白细胞介素-31 （IL-31）是一种新型的T细胞来源的细胞因子，在转基因小鼠中诱导严重的瘙痒和皮炎，并通过由白细胞介素-31受体a （IL-31RA）和肿瘤抑制素M受体（OSMR）组成的异二聚体受体发出信号。在最近的一项研究中，申请人表明，与“低或非瘙痒性”银屑病皮肤炎症相比，IL-31在“瘙痒性”特应性中显着过度表达。在结节性痒疹中检测到最高的IL-31水平，结节性痒疹是皮肤炎症的瘙痒形式之一。在体内，葡萄球菌超抗原在特应性个体中迅速诱导IL-31表达。在体外，葡萄球菌肠毒素B而不是病毒或Th1和Th2细胞因子诱导白细胞中的IL-31。此外，与对照组相比，特应性皮炎患者的活化白细胞表达IL-31的水平显著升高。IL-31RA在代表皮肤感觉神经元细胞体所在部位的背根神经节中表达最丰富。我们的研究结果为特应性皮炎患者的葡萄球菌定植、随后的T细胞募集/激活和瘙痒诱导之间提供了新的联系。综上所述，IL-31可能是抗瘙痒药物开发的一个新的、有希望的靶点。

Pruritus is a dominant symptom of atopic skin inflammation and severely affects the quality of life of affected patients. Despite recent advances in the understanding of the immunopathogenesis of atopic skin inflammation, the underlying mechanisms of pruritus are still poorly understood. Recently, it has been shown that interleukin-31 (IL-31), a novel T cellderived cytokine, induces severe pruritus and dermatitis in transgenic mice, and signals through a heterodimeric receptor composed of interleukin-31 receptor A (IL-31RA) and oncostatin M receptor (OSMR). In a recent study, the applicants showed that IL-31 was significantly overexpressed in `pruritic’ atopic compared to ‘low- or non-pruritic’ psoriatic skin inflammation. Highest IL-31 levels were detected in prurigo nodularis, representing one of the pruritic forms of skin inflammation. In-vivo, staphylococcal superantigen rapidly induced IL-31 expression in atopic individuals. In-vitro, staphylococcal enterotoxin B but not viruses or Th1 and Th2 cytokines induced IL-31 in leukocytes. Furthermore, activated leukocytes of atopic dermatitis patients expressed IL-31 at significantly higher levels, as compared to control subjects. IL-31RA showed most abundant expression in dorsal root ganglia representing the site where the cell bodies of cutaneous sensory neurons reside. Our findings provide a new link between staphylococcal colonization, subsequent T cell recruitment/activation and pruritus induction in atopic dermatitis patients. Taken together, IL-31 may represent a novel and promising target for antipruritic drug development.