Granuloma annulare skin profile shows activation of T-helper cell type 1, T-helper cell type 2, and Janus kinase pathways.,Journal of the American Academy of Dermatology

当前位置： X-MOL 学术 › J. Am. Acad. Dermatol. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Granuloma annulare skin profile shows activation of T-helper cell type 1, T-helper cell type 2, and Janus kinase pathways.
Journal of the American Academy of Dermatology ( IF 12.8 ) Pub Date : 2019-12-20 , DOI: 10.1016/j.jaad.2019.12.028
Michelle S Min ₁ , Jianni Wu ₂ , Helen He ₁ , Juan Luis Sanz-Cabanillas ₃ , Ester Del Duca ₄ , Ning Zhang ₁ , Yael Renert-Yuval ₅ , Ana B Pavel ₁ , Mark Lebwohl ₁ , Emma Guttman-Yassky ₆

Affiliation

Background

Granuloma annulare (GA) is an inflammatory skin disorder. Localized GA is often self-resolving, but generalized GA is often recalcitrant to treatments. There are no targeted treatments for GA, largely due to lack of mechanistic understanding. Recently, tumor necrosis factor antagonism showed promise in GA, suggesting an underlying immune pathogenesis.

Objective

To elucidate the immune pathogenesis and identify potential therapeutic targets for GA.

Methods

Lesional and nonlesional skin biopsy samples were obtained from patients with GA and evaluated for a large array of inflammatory markers compared with inflammatory markers from normal skin of healthy individuals.

Results

We found differential expression of many inflammatory genes compared with normal skin. These genes were associated with T-helper (Th) cell type 1/innate immunity (tumor necrosis factor-α, interleukin [IL]-1β, IL-12/23p40, signal transducer and activator of transcription 1, chemokine [C-X-C motif] ligand 9/10), Janus kinase signaling, and Th2 (IL-4, IL-31, chemokine (C-C motif) ligands 17 and 18; P < .05). Unexpectedly, IL-4 showed significant upregulation in GA lesional skin vs control skin (15,600-fold change).

Limitations

Limited sample size.

Conclusions

Our findings shed light on the inflammatory pathways of GA, supporting the notion that immune mechanisms could be driving disease, as suggested by the promising data of tumor necrosis factor-α inhibitors in GA. The significant Janus kinase and particularly Th2 signaling in GA advocates for the investigation of specific Janus kinase- and Th2- targeted drug therapy.

中文翻译：

环形肉芽肿的皮肤轮廓显示T型辅助细胞1型，T型辅助细胞2型和Janus激酶途径被激活。

背景

环形肉芽肿（GA）是一种炎症性皮肤病。局限性GA通常是自我解决的，但广义GA通常对治疗不利。目前尚无针对GA的靶向治疗方法，这主要是由于缺乏对机械的理解。最近，肿瘤坏死因子拮抗作用在GA中显示出前景，表明潜在的免疫发病机制。

客观的

阐明免疫发病机理并确定GA的潜在治疗靶标。

方法

从GA患者获得病变和非病变皮肤活检样品，并与健康个体正常皮肤的炎症标志物进行比较，评估了多种炎症标志物。

结果

我们发现与正常皮肤相比，许多炎症基因的差异表达。这些基因与1型T辅助（Th）细胞/先天免疫相关（肿瘤坏死因子-α，白介素[IL]-1β，IL-12 / 23p40，信号转导子和转录激活因子1，趋化因子[CXC]基序）。配体9/10），Janus激酶信号传导和Th2（IL-4，IL-31，趋化因子（CC基序）配体17和18; P <.05）。出乎意料的是，IL-4相对于对照皮肤在GA病变皮肤中显示出明显的上调（变化为15600倍）。