Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa.
Single-Cell RNA Sequencing Reveals Cellular and Transcriptional Changes Associated With M1 Macrophage Polarization in Hidradenitis Suppurativa.
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DOI：
10.3389/fmed.2021.665873
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发表时间：
2021
影响因子：
3.9
通讯作者：
MacLeod AS
中科院分区：
文献类型：
--
作者：
Mariottoni P;Jiang SW;Prestwood CA;Jain V;Suwanpradid J;Whitley MJ;Coates M;Brown DA;Erdmann D;Corcoran DL;Gregory SG;Jaleel T;Zhang JY;Harris-Tryon TA;MacLeod AS
化脓性汗腺炎 (HS) 是一种慢性炎症性皮肤病，其特征是毛囊和汗腺密度高的区域反复出现脓肿、结节和窦道。这些窦道可出现脓性引流和疤痕形成。多种免疫途径的失调导致热射病发病机制的复杂性，并可能解释热射病患者治疗反应的异质性。我们使用转录组学方法，包括单细胞测序和蛋白质分析，描述了 HS 病变的先天炎症景观。我们通过对 HS 皮肤、糖尿病足溃疡 (DFU) 和正常愈合伤口炎症阶段数据集中的差异表达基因 (DEG) 进行转录组重叠分析，确定了干扰素 (IFN) 和抗菌防御信号相关基因的共同上调。 HS 和 DFU 特异性 DEG 之间的重叠分析揭示了与单核细胞/巨噬细胞功能相关的基因特征的富集。单细胞 RNA 测序进一步揭示单核细胞/巨噬细胞极化为促炎性 M1 样表型，并增强效应功能，包括抗病毒免疫、吞噬作用、呼吸爆发和抗体依赖性细胞毒性。具体来说，我们确定了 STAT1/IFN 信号轴和相关的 IFN 刺激基因是单核细胞/巨噬细胞失调的核心参与者。我们的数据表明，单核细胞/巨噬细胞是 HS 发病机制中潜在的关键参与者，其通路可作为 HS 治疗的治疗靶点和生物标志物。
Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent abscesses, nodules, and sinus tracts in areas of high hair follicle and sweat gland density. These sinus tracts can present with purulent drainage and scar formation. Dysregulation of multiple immune pathways drives the complexity of HS pathogenesis and may account for the heterogeneity of treatment response in HS patients. Using transcriptomic approaches, including single-cell sequencing and protein analysis, we here characterize the innate inflammatory landscape of HS lesions. We identified a shared upregulation of genes involved in interferon (IFN) and antimicrobial defense signaling through transcriptomic overlap analysis of differentially expressed genes (DEGs) in datasets from HS skin, diabetic foot ulcers (DFUs), and the inflammatory stage of normal healing wounds. Overlap analysis between HS- and DFU-specific DEGs revealed an enrichment of gene signatures associated with monocyte/macrophage functions. Single-cell RNA sequencing further revealed monocytes/macrophages with polarization toward a pro-inflammatory M1-like phenotype and increased effector function, including antiviral immunity, phagocytosis, respiratory burst, and antibody-dependent cellular cytotoxicity. Specifically, we identified the STAT1/IFN-signaling axis and the associated IFN-stimulated genes as central players in monocyte/macrophage dysregulation. Our data indicate that monocytes/macrophages are a potential pivotal player in HS pathogenesis and their pathways may serve as therapeutic targets and biomarkers in HS treatment.
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影响因子：
7.3
作者：
Clayton K;Vallejo AF;Davies J;Sirvent S;Polak ME
通讯作者：
Polak ME
影响因子：
6.4
作者：
Collin M;Bigley V
通讯作者：
Bigley V
影响因子：
13.8
作者：
Frew JW;Navrazhina K;Grand D;Sullivan-Whalen M;Gilleaudeau P;Garcet S;Ungar J;Krueger JG
通讯作者：
Krueger JG
影响因子：
14.2
作者：
Annunziato, Francesco;Romagnani, Chiara;Romagnani, Sergio
通讯作者：
Romagnani, Sergio
影响因子：
6.7
作者：
Coates, Margaret;Blanchard, Sarah;Macleod, Amanda S.
通讯作者：
Macleod, Amanda S.