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。尽管最近在特应性皮肤炎症的免疫发病机制的理解方面取得了进展，但瘙痒的潜在机制仍然知之甚少。近年来研究发现，白细胞介素-31（IL-31）是一种新的T细胞源性细胞因子，可诱导转基因小鼠产生严重的瘙痒和皮炎，其信号转导途径是由白细胞介素-31受体A（IL-31 RA）和抑瘤素M受体（OSMR）组成的异源二聚体受体。在最近的一项研究中，申请人表明，与“低-或非-过敏性”银屑病皮肤炎症相比，IL-31在“过敏性”特应性中显著过表达。最高的IL-31水平在结节性黑热病中检测到，代表皮肤炎症的一种炎性形式。在体内，葡萄球菌超抗原快速诱导过敏性个体中的IL-31表达。在体外，葡萄球菌肠毒素B而不是病毒或Th 1和Th 2细胞因子诱导白细胞中的IL-31。此外，与对照受试者相比，特应性皮炎患者的活化白细胞以显著更高的水平表达IL-31。IL-31 RA在背根神经节中表现出最丰富的表达，背根神经节代表皮肤感觉神经元的细胞体所在的部位。我们的研究结果提供了一个新的联系葡萄球菌定植，随后的T细胞募集/激活和瘙痒诱导特应性皮炎患者。综上所述，IL-31可能代表了一个新的和有前途的抗炎症药物开发的目标。

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.