Moran Barry, Sweeney Cheryl M, Hughes Rosalind, Malara Anna, Kirthi Shivashini, Tobin Anne-Marie, Kirby Brian, Fletcher Jean M
School of Biochemistry and Immunology, Trinity Biomedical Sciences Institute, Trinity College Dublin, Ireland.
Dermatology Research, Education and Research Centre, St. Vincent's University Hospital, Dublin 4, Ireland.
J Invest Dermatol. 2017 Nov;137(11):2389-2395. doi: 10.1016/j.jid.2017.05.033. Epub 2017 Jun 23.
Hidradenitis suppurativa (HS) is a chronic, inflammatory, and debilitating disease of hair follicles with 1-4% prevalence and high morbidity. There is a dearth of information on the pathogenesis and immune dysregulation underlying HS; therefore, we carried out a detailed analysis of skin-infiltrating T cells. Cells isolated from skin biopsy samples and blood from HS patients and healthy control subjects were analyzed by 16-parameter flow cytometry to provide detailed profiles of CD4 T-cell subsets. We observed substantial infiltration of inflammatory T cells with a striking T helper (Th) type 17-skewed cytokine profile in HS skin; these cells expressed the Th17 lineage marker CD161 and IL-17, as well as proinflammatory cytokines GM-CSF, IL-22, IFN-γ, and tumor necrosis factor. Regulatory T cells were also enriched in HS lesional skin; however, the ratio of Th17 to regulatory T cells was nonetheless highly dysregulated in favor of Th17 cells. In contrast, lesional skin from anti-tumor necrosis factor-treated HS patients who showed substantial clinical improvement exhibited a significant reduction in the frequency of Th17 cells and normalization of the Th17 to regulatory T cell ratio. These data suggest that inhibition of pathogenic IL-17 via tumor necrosis factor blockade is associated with improvement in immune dysregulation in HS and may provide a rationale for targeting IL-17 in the disease.
化脓性汗腺炎（HS）是一种毛囊的慢性、炎症性且使人衰弱的疾病，患病率为1%-4%，发病率较高。关于HS潜在的发病机制和免疫失调的信息匮乏；因此，我们对皮肤浸润性T细胞进行了详细分析。通过16参数流式细胞术分析从HS患者和健康对照者的皮肤活检样本及血液中分离出的细胞，以提供CD4 T细胞亚群的详细概况。我们观察到在HS皮肤中有大量炎症性T细胞浸润，其细胞因子谱明显偏向辅助性T细胞（Th）17型；这些细胞表达Th17谱系标志物CD161和IL-17，以及促炎细胞因子GM-CSF、IL-22、IFN-γ和肿瘤坏死因子。调节性T细胞在HS病变皮肤中也有所富集；然而，Th17细胞与调节性T细胞的比例仍然高度失调，偏向于Th17细胞。相比之下，接受抗肿瘤坏死因子治疗且临床症状有显著改善的HS患者的病变皮肤中，Th17细胞频率显著降低，Th17细胞与调节性T细胞的比例恢复正常。这些数据表明，通过肿瘤坏死因子阻断抑制致病性IL-17与HS免疫失调的改善有关，可能为该疾病中靶向IL-17提供理论依据。
