Laboratory for Investigative Dermatology, The Rockefeller University, New York, New York, USA.
Pediatric Dermatology Unit, Schneider Children's Medical Center of Israel, Petah Tikva, Israel and Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Exp Dermatol. 2024 Jul;33(7):e15129. doi: 10.1111/exd.15129.
Hidradenitis suppurativa (HS) is an inflammatory skin disease characterized by painful nodules, abscesses and purulent secretions in intertriginous regions. Intense pruritus frequently accompanies HS lesions, adding further discomfort for patients. While Th17 pathway activation is implicated in HS pathogenesis, disease mechanisms are still not fully understood, and therapeutics are lacking. Previous reports raise a potential role for eosinophils in HS, showing a strong association of eosinophil levels with disease severity. To investigate eosinophils in HS, we recruited patients and matched healthy controls and then performed flow-cytometry studies, eosinophil stimulation assays, and lesional skin staining for eosinophils. We found that HS patients reported similar levels of pain and itch. Compared to matched controls, HS blood exhibited decreased mature eosinophils and increased numbers of immature eosinophils, coupled with a significant increase in dermal eosinophilic infiltrates. Additionally, IL-17RA eosinophils were highly and significantly correlated with multiple HS-related clinical scores. In both stimulated and unstimulated conditions, HS eosinophils showed an inflammatory phenotype versus controls, including an increase in costimulatory T- and B-cell markers (e.g. CD5 and CD40) following all stimulations (TNFα/IL-17A/IL-17F). These findings highlight the significance of pruritus in HS and suggest a higher turnover of eosinophils in HS blood, potentially due to the consumption of eosinophils in skin lesions. Our data delineate the features and functions of eosinophils in HS and suggest that eosinophils participate in disease pathogenesis, advancing Th17-related inflammation. Further studies are needed to investigate eosinophils' response to current HS treatments and their potential as a therapeutic target in the disease.
化脓性汗腺炎(HS)是一种炎症性皮肤病,其特征是在皱褶部位出现疼痛性结节、脓肿和脓性分泌物。HS 病变常伴有剧烈瘙痒,进一步加重患者的不适。虽然 Th17 通路的激活与 HS 的发病机制有关,但疾病机制仍不完全清楚,且缺乏治疗方法。先前的报告提出了嗜酸性粒细胞在 HS 中的潜在作用,表明嗜酸性粒细胞水平与疾病严重程度密切相关。为了研究 HS 中的嗜酸性粒细胞,我们招募了患者和匹配的健康对照者,然后进行了流式细胞术研究、嗜酸性粒细胞刺激试验以及嗜酸性粒细胞在皮损皮肤中的染色。我们发现 HS 患者报告的疼痛和瘙痒程度相似。与匹配的对照组相比,HS 血液中成熟的嗜酸性粒细胞减少,不成熟的嗜酸性粒细胞增多,同时真皮中嗜酸性粒细胞浸润明显增加。此外,IL-17RA 嗜酸性粒细胞与多个 HS 相关的临床评分高度显著相关。在刺激和非刺激条件下,HS 嗜酸性粒细胞与对照组相比表现出炎症表型,包括所有刺激(TNFα/IL-17A/IL-17F)后共刺激 T 细胞和 B 细胞标志物(如 CD5 和 CD40)增加。这些发现强调了 HS 中瘙痒的重要性,并提示 HS 血液中嗜酸性粒细胞的更新率较高,可能是由于皮肤病变中嗜酸性粒细胞的消耗。我们的数据描绘了 HS 中嗜酸性粒细胞的特征和功能,并表明嗜酸性粒细胞参与了疾病的发病机制,促进了 Th17 相关炎症。需要进一步研究来探讨嗜酸性粒细胞对当前 HS 治疗的反应及其作为该疾病治疗靶点的潜力。