IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function.
IL-31-Driven Skin Remodeling Involves Epidermal Cell Proliferation and Thickening That Lead to Impaired Skin-Barrier Function.
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DOI：
10.1371/journal.pone.0161877
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Madala SK
中科院分区：
文献类型：
--
作者：
Singh B;Jegga AG;Shanmukhappa KS;Edukulla R;Khurana Hershey GH;Medvedovic M;Dillon SR;Madala SK
白细胞介素-31（IL-31）是一种2型辅助性T细胞衍生的细胞因子，最近已显示其在多种皮肤和肺部慢性疾病中引起严重炎症和组织重塑。IL-31在过敏性和炎性疾病中上调，包括特应性皮炎、哮喘、皮肤T细胞淋巴瘤和过敏性鼻炎，以及自身免疫性疾病如系统性红斑狼疮。IL-31在T细胞中的过度表达导致严重的炎症，其组织学特征类似于特应性皮炎患者的皮肤病变。然而，在皮肤疾病中IL 31驱动的病理性重塑所涉及的分子机制在很大程度上仍然未知。在这里，我们研究了IL-31在皮肤损伤中的作用，作为皮内注射重组IL-31到小鼠体内的结果。值得注意的是，IL-31足以增加表皮基底细胞增殖和表皮皮肤层增厚。我们的研究结果表明，随着IL-31长期给药到皮肤中，经表皮水分流失逐渐增加。此外，对皮肤转录组的分析表明参与表皮细胞增殖、表皮增厚和机械完整性的转录物显著增加。总之，我们的研究结果表明，IL-31信号传导在表皮细胞增殖和增厚中起重要作用，这两者一起可能导致皮肤病理性重塑中皮肤屏障功能受损。
Interleukin-31 (IL-31) is a type 2 helper T-cell-derived cytokine that has recently been shown to cause severe inflammation and tissue remodeling in multiple chronic diseases of the skin and lungs. IL-31 is upregulated in allergic and inflammatory diseases, including atopic dermatitis, asthma, cutaneous T-cell lymphomas, and allergic rhinitis, as well as autoimmune diseases such as systemic erythematosus. Overexpression of IL-31 in T cells causes severe inflammation, with histological features similar to skin lesions of patients with atopic dermatitis. However, the molecular mechanisms involved in IL31-driven pathological remodeling in skin diseases remain largely unknown. Here, we studied the role of IL-31 in skin damage as a result of intradermal administration of recombinant IL-31 into mice. Notably, IL-31 was sufficient to increase epidermal basal-cell proliferation and thickening of the epidermal skin layer. Our findings demonstrate a progressive increase in transepidermal water loss with chronic administration of IL-31 into the skin. Further, analysis of the skin transcriptome indicates a significant increase in the transcripts involved in epidermal-cell proliferation, epidermal thickening, and mechanical integrity. In summary, our findings demonstrate an important role for IL-31 signaling in epidermal cell proliferation and thickening that together may lead to impaired skin-barrier function in pathological remodeling of the skin.