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在化脓性汗腺炎中发现一种新的辅助性 T 细胞 17 细胞因子:白细胞介素-26 的抗菌和促炎作用。

A new T helper 17 cytokine in hidradenitis suppurativa: antimicrobial and proinflammatory role of interleukin-26.

机构信息

Department of Clinical Medicine and Surgery, University of Naples Federico II, Via Pansini 5, 80131, Naples, Italy.

Department of Experimental Medicine, University of Campania 'Luigi Vanvitelli', Naples, Italy.

出版信息

Br J Dermatol. 2019 Nov;181(5):1038-1045. doi: 10.1111/bjd.17854. Epub 2019 Jun 23.

DOI:10.1111/bjd.17854
PMID:30829398
Abstract

BACKGROUND

Interleukin (IL)-26 is a signature T helper 17 cytokine described as a proinflammatory and antimicrobial mediator. So far, IL-26 has been reported in several immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders is poorly known.

OBJECTIVES

To investigate the role of IL-26 in hidradenitis suppurativa (HS), through its involvement in antimicrobial activity.

METHODS

IL-26 was assessed in patients with HS through gene expression and protein analysis at skin and circulating levels. Ex vivo HS organ skin cultures, together with IL-26 antibody treatment, were performed to determine the IL-26 activity. Peripheral blood mononuclear cells (PBMCs) from patients with HS and healthy controls were either silenced or not with IL-26 small interfering (si)RNA in order to measure its antimicrobial, cytotoxic and phagocytic activities against Staphylococcus aureus.

RESULTS

Firstly, we observed that IL-26 is able to modulate the proinflammatory response at the immune cell level. IL-26 was increased in the plasma of patients with HS compared with healthy controls. Subsequently, we explored the bactericidal, cytotoxic and phagocytic activities of PBMCs against S. aureus in patients with HS and healthy controls. These activities were lower in patients with HS than in controls. Remarkably, the killing activities were reduced when healthy control PBMCs were transfected with IL-26 siRNA. However, the transfection did not affect the killing activity of HS PBMCs, supporting the idea that IL-26 lacks efficacy in HS.

CONCLUSIONS

Our findings suggest that infection susceptibility in HS might be related to IL-26. Although the role of bacteria remains controversial in HS, this paper supports that there is a defect of antimicrobial response in these patients. What's already known about this topic? Interleukin (IL)-26 is a T helper 17 cytokine described as an antimicrobial and proinflammatory mediator. IL-26 has been reported in immune-mediated inflammatory diseases, but its involvement in inflammatory skin disorders remains unclear. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disorder characterized by deficiency of IL-20 and IL-22 (a close homologue of IL-26), which causes antimicrobial peptide pauperization leading to severe and recurrent skin infections. What does this study add? IL-26 plasma levels are higher in patients with HS than in healthy control individuals. The antimicrobial activity of IL-26 might be ineffective in patients with HS. What is the translational message? Cutaneous antimicrobial incompetence in HS could be related to IL-26.

摘要

背景

白细胞介素(IL)-26 是一种标志性的辅助性 T 细胞 17 细胞因子,被描述为一种促炎和抗微生物介质。到目前为止,IL-26 已在几种免疫介导的炎症性疾病中报道,但它在炎症性皮肤疾病中的作用知之甚少。

目的

通过其在抗微生物活性中的作用,研究 IL-26 在化脓性汗腺炎(HS)中的作用。

方法

通过皮肤和循环水平的基因表达和蛋白分析评估 HS 患者的 IL-26。进行 HS 器官皮肤培养物的离体实验,并结合 IL-26 抗体治疗,以确定 IL-26 的活性。为了测量其对金黄色葡萄球菌的抗微生物、细胞毒性和吞噬作用,用 IL-26 小干扰(si)RNA 对 HS 患者和健康对照者的外周血单核细胞(PBMCs)进行沉默或不沉默处理。

结果

首先,我们观察到 IL-26 能够在免疫细胞水平上调节促炎反应。与健康对照组相比,HS 患者的血浆中 IL-26 增加。随后,我们研究了 HS 患者和健康对照组的 PBMCs 对金黄色葡萄球菌的杀菌、细胞毒性和吞噬作用。与对照组相比,这些活动在 HS 患者中较低。值得注意的是,当用 IL-26 siRNA 转染健康对照者的 PBMCs 时,杀伤活性降低。然而,转染并不影响 HS PBMCs 的杀伤活性,这支持了 IL-26 在 HS 中缺乏疗效的观点。

结论

我们的研究结果表明,HS 中的感染易感性可能与 IL-26 有关。尽管细菌在 HS 中的作用仍存在争议,但本文支持这些患者存在抗微生物反应缺陷的观点。

关于这个主题已经知道些什么?白细胞介素(IL)-26 是一种辅助性 T 细胞 17 细胞因子,被描述为一种抗微生物和促炎介质。IL-26 已在免疫介导的炎症性疾病中报道,但它在炎症性皮肤疾病中的作用仍不清楚。化脓性汗腺炎(HS)是一种慢性炎症性皮肤疾病,其特征是缺乏 IL-20 和 IL-22(IL-26 的密切同源物),这导致抗菌肽匮乏,导致严重和复发性皮肤感染。

本研究增加了哪些新内容?HS 患者的 IL-26 血浆水平高于健康对照组。IL-26 的抗微生物活性在 HS 患者中可能无效。

这有什么转化意义?HS 中的皮肤抗微生物无能可能与 IL-26 有关。

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