Intrinsic Defect in Keratinocyte Function Leads to Inflammation in Hidradenitis Suppurativa
Intrinsic Defect in Keratinocyte Function Leads to Inflammation in Hidradenitis Suppurativa
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DOI：
10.1016/j.jid.2016.04.036
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发表时间：
2016-09-01
影响因子：
6.5
通讯作者：
Hue, Sophie
中科院分区：
文献类型：
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作者：
Hotz, Claire;Boniotto, Michele;Hue, Sophie
化脓性汗腺炎（HS）是一种慢性、炎症性、衰弱性的皮肤滤泡性疾病。尽管在普通人群中有很高的患病率，但对HS的生理病理仍知之甚少。使用抗生素和免疫抑制剂进行治疗表明对微生物群的免疫反应失调。通过细胞和基因表达分析，我们发现HS患者病灶周围和病变皮肤中分泌IL-17和ifn - γ的浸润性CD4(+) T细胞数量增加。相比之下，分泌il -22的CD4(+) T细胞在HS病变中不富集，而HS患者血液中CD4(+) T细胞数量增加。我们发现，从HS患者的毛囊中分离的角质形成细胞分泌更多的IL-1 β、IP-10和趋化因子（C-C基序）配体5 (RANTES)，无论是组成性刺激还是模式识别受体刺激。此外，它们还显示出一种独特的抗菌肽生产模式。这些发现指出了HS中角质形成细胞的功能缺陷，导致容易产生炎症反应的平衡。这可能有利于细菌感染和慢性炎症的宽松环境，这是HS患者临床结果的特征。
Hidradenitis suppurativa (HS) is a chronic, inflammatory, debilitating, follicular disease of the skin. Despite a high prevalence in the general population, the physiopathology of HS remains poorly understood. The use of antibiotics and immunosuppressive agents for therapy suggests a deregulated immune response to microflora. Using cellular and gene expression analyses, we found an increased number of infiltrating CD4(+) T cells secreting IL-17 and IFN-gamma in perilesional and lesional skin of patients with HS. By contrast, IL-22-secreting CD4(+) T cells are not enriched in HS lesions contrasting with increased number of those cells in the blood of patients with HS. We showed that keratinocytes isolated from hair follicles of patients with HS secreted significantly more IL-1 beta, IP-10, and chemokine (C-C motif) ligand 5 (RANTES) either constitutively or on pattern recognition receptor stimulations. In addition, they displayed a distinct pattern of antimicrobial peptide production. These findings point out a functional defect of keratinocytes in HS leading to a balance prone to inflammatory responses. This is likely to favor a permissive environment for bacterial infections and chronic inflammation characterizing clinical outcomes in patients with HS.