Department of Dermatology and Venereology, Aarhus University Hospital, 8200 Aarhus, Denmark.
Int J Mol Sci. 2023 Nov 30;24(23):17014. doi: 10.3390/ijms242317014.
Hidradenitis suppurativa is a chronic inflammatory skin disease with limited treatment options. The poorly understood pathogenesis hinders the development of effective treatments; therefore, a pressing need exists to further elucidate the molecular mechanisms in hidradenitis suppurativa. This study investigated the underlying inflammatory pathways and cell types in hidradenitis suppurativa using transcriptomic approaches with RNA sequencing of lesional and non-lesional skin biopsies from hidradenitis suppurativa, which was jointly analyzed with previously published transcriptomic data from atopic dermatitis and psoriasis patients. The differential expression and pathway enrichment analyses demonstrated the activation of multiple inflammatory processes, including the innate and adaptive immune systems, implicated in the hidradenitis suppurativa pathogenesis. In agreement, hidradenitis suppurativa exhibited a unique and heterogeneous cell type signature involving lymphoid and myeloid cells such as B cells and macrophages. Furthermore, hidradenitis suppurativa displayed increased expression of T1/2/17 signatures with no predominant T signatures unlike psoriasis (T1/17) and atopic dermatitis (T2). In summary, our study provides molecular insights into the pathomechanisms in hidradenitis suppurativa, revealing a strong and widespread immune activation, which may benefit from treatment strategies offering a broad immunomodulation of various key inflammatory pathways. Our data not only corroborate previously reported findings but also enhance our understanding of the immune dysregulation in hidradenitis suppurativa, uncovering novel and potential therapeutic targets.
化脓性汗腺炎是一种慢性炎症性皮肤病，治疗选择有限。发病机制理解不足阻碍了有效治疗方法的发展；因此，迫切需要进一步阐明化脓性汗腺炎的分子机制。本研究采用 RNA 测序技术，对化脓性汗腺炎患者皮损和非皮损皮肤活检组织进行转录组分析，联合分析了特应性皮炎和银屑病患者的先前发表的转录组数据，以此研究化脓性汗腺炎的潜在炎症途径和细胞类型。差异表达和通路富集分析表明，多种炎症过程被激活，包括先天和适应性免疫系统，这与化脓性汗腺炎的发病机制有关。一致的是，化脓性汗腺炎表现出独特且异质的细胞类型特征，涉及淋巴细胞和髓样细胞，如 B 细胞和巨噬细胞。此外，与银屑病（T1/17）和特应性皮炎（T2）不同，化脓性汗腺炎显示出 T1/2/17 特征的表达增加，而没有占主导地位的 T 特征。总之，我们的研究为化脓性汗腺炎的发病机制提供了分子见解，揭示了强烈而广泛的免疫激活，这可能受益于提供各种关键炎症途径广泛免疫调节的治疗策略。我们的数据不仅证实了先前报道的发现，而且还增强了我们对化脓性汗腺炎免疫失调的理解，揭示了新的潜在治疗靶点。
