MIR31HG Modulates IL-4 Secretion by Keratinocytes and M2-Like Macrophage Polarization to Promote Local Immunosuppression in Condyloma Acuminata.

IF 2.8 4区医学 Q3 DERMATOLOGY

Skin Research and Technology Pub Date : 2026-09-01 DOI:10.1111/srt.70384

Xiaohang Xie, Lian Liu, Huayu Huang, Yuchun Cao, Zhichao Gu

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引用次数: 0

Abstract

Background: Condyloma acuminata (CA) is clinically associated with localized immunosuppression, yet the mechanisms underlying HPV-mediated immune evasion remain poorly understood. Although the long non-coding RNA MIR31HG has been implicated in inflammatory regulation, its role in the immunosuppressive microenvironment of CA has not been explored.

Methods: We analyzed MIR31HG expression in CA and normal skin tissues. HaCaT cells infected with CA-derived HPV6/11 (HPV6/11-HaCaT) and controls treated with skin-derived supernatant were established to explore the association between HPV6/11 and MIR31HG. The HPV6/11-HaCaT model was further used to investigate the effects of MIR31HG on cytokine secretion and macrophage polarization. Bioinformatic prediction, dual-luciferase reporter assays and rescue experiments targeting PI3K/AKT and IL-4 signaling were performed to investigate the underlying molecular mechanisms.

Results: MIR31HG was significantly upregulated in CA keratinocytes compared with normal skin. In vitro, HPV6/11 induced the expression of MIR31HG. Functional studies demonstrated that MIR31HG induced a cytokine shift in HPV6/11-HaCaT cells, characterized by elevated anti-inflammatory IL-4 and reduced pro-inflammatory mediators, including TNF-α, IFN-β, IL-6 and IL-8. This IL-4 surge promoted M2-like macrophage polarization, a hallmark of immunosuppression, thereby contributing to an immunosuppressive microenvironment in CA. Mechanistically, MIR31HG functioned as a ceRNA for miR-214-3p in HPV6/11-HaCaT cells, leading to enhanced PTEN expression and subsequent suppression of the PI3K/AKT pathway, thereby contributing to an immunosuppressive cytokine profile and M2-like macrophage polarization.

Conclusion: Our findings highlight the immunomodulatory role of keratinocytes in CA and highlight the MIR31HG/IL-4 axis as a novel therapeutic target for CA, bridging mechanistic insight with translational potential.

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MIR31HG调节角质形成细胞分泌IL-4和m2样巨噬细胞极化促进尖锐湿疣局部免疫抑制

背景：临床上尖锐湿疣（CA）与局部免疫抑制有关，但hpv介导的免疫逃避机制尚不清楚。虽然长链非编码RNA MIR31HG参与炎症调节，但其在CA免疫抑制微环境中的作用尚未被探索。方法：分析CA和正常皮肤组织中MIR31HG的表达。建立ca源性HPV6/11 （HPV6/11-HaCaT）感染HaCaT细胞和皮肤源性上清处理的对照组，探讨HPV6/11与MIR31HG之间的关系。采用HPV6/11-HaCaT模型进一步研究MIR31HG对细胞因子分泌和巨噬细胞极化的影响。通过生物信息学预测、双荧光素酶报告基因检测和靶向PI3K/AKT和IL-4信号通路的拯救实验来研究潜在的分子机制。结果：与正常皮肤相比，CA角质形成细胞中MIR31HG明显上调。在体外，HPV6/11诱导MIR31HG的表达。功能研究表明，MIR31HG诱导HPV6/11-HaCaT细胞的细胞因子转移，其特征是抗炎IL-4升高，促炎介质包括TNF-α、IFN-β、IL-6和IL-8降低。这种IL-4激增促进了m2样巨噬细胞极化，这是免疫抑制的标志，从而促进了CA的免疫抑制微环境。机制上，MIR31HG在HPV6/11-HaCaT细胞中作为miR-214-3p的ceRNA，导致PTEN表达增强，随后抑制PI3K/AKT通路，从而促进免疫抑制细胞因子谱和m2样巨噬细胞极化。结论：我们的研究结果突出了角化细胞在CA中的免疫调节作用，并突出了MIR31HG/IL-4轴作为CA的新治疗靶点，将机制与翻译潜力联系起来。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Skin Research and Technology 医学-皮肤病学

CiteScore

3.30

自引率

9.10%

发文量

审稿时长

6-12 weeks

期刊介绍： Skin Research and Technology is a clinically-oriented journal on biophysical methods and imaging techniques and how they are used in dermatology, cosmetology and plastic surgery for noninvasive quantification of skin structure and functions. Papers are invited on the development and validation of methods and their application in the characterization of diseased, abnormal and normal skin. Topics include blood flow, colorimetry, thermography, evaporimetry, epidermal humidity, desquamation, profilometry, skin mechanics, epiluminiscence microscopy, high-frequency ultrasonography, confocal microscopy, digital imaging, image analysis and computerized evaluation and magnetic resonance. Noninvasive biochemical methods (such as lipids, keratin and tissue water) and the instrumental evaluation of cytological and histological samples are also covered. The journal has a wide scope and aims to link scientists, clinical researchers and technicians through original articles, communications, editorials and commentaries, letters, reviews, announcements and news. Contributions should be clear, experimentally sound and novel.