The IL-1 Pathway Is Hyperactive in Hidradenitis Suppurativa and Contributes to Skin Infiltration and Destruction
The IL-1 Pathway Is Hyperactive in Hidradenitis Suppurativa and Contributes to Skin Infiltration and Destruction
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DOI：
10.1016/j.jid.2018.11.018
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发表时间：
2019-06-01
影响因子：
6.5
通讯作者：
Sabat, Robert
中科院分区：
文献类型：
--
作者：
Witte-Haendel, Ellen;Wolk, Kerstin;Sabat, Robert
化脓性汗腺炎（HS）（也称为反向痤疮）是一种慢性炎性疾病，其特征在于疼痛的化脓性皮肤病变和皮肤结构的进行性破坏。尽管患者的负担很高，但HS改变的致病途径仍然不清楚。当我们检查HS细胞因子模式时，IL-1 β是一种非常突出的细胞因子，甚至与银屑病病变相比也过表达。对各种细胞类型中IL-1 β诱导的转录组的分析显示重叠的谱，引起免疫细胞浸润和细胞外基质降解的分子以及包括IL-6、IL-32和IL-36的特异性细胞因子的上调。与细胞IL-1受体水平相匹配，真皮成纤维细胞表现出最强和最广泛的IL-1 β反应，这与其他细胞因子没有明显共享或加强。IL-1 β信号特异性地存在于HS病变中，并且可以通过应用IL-1受体拮抗剂来逆转。在HS中搜索与IL-1 β途径活性相关的血液参数，鉴定了血清淀粉样蛋白A，其在肝细胞中由IL-1 β和IL-6协同诱导。因此，HS患者血清淀粉样蛋白A水平的升高与炎症性皮肤改变的程度呈正相关。总之，IL-1 β途径代表了一种致病级联反应，其活性可以通过血液SAA水平进行治疗靶向和监测。
Hidradenitis suppurativa (HS) (also designated acne inversa) is a chronic inflammatory disease characterized by painful purulent skin lesions and progressive destruction of skin architecture. Despite the high burden for the patients, pathogenetic pathways underlying HS alterations remain obscure. When we examined the HS cytokine pattern, IL-1 beta turned out to be a highly prominent cytokine, overexpressed even compared with psoriatic lesions. Analyses of IL-1 beta-induced transcriptome in various cell types showed overlapping profiles, with upregulations of molecules causing immune cell infiltration and extracellular matrix degradation, and of specific cytokines including IL-6, IL-32, and IL-36. Matching cellular IL-1 receptor levels, dermal fibroblasts showed both the strongest and broadest IL-1 beta response, which was not clearly shared or strengthened by other cytokines. The IL-1 beta signature was specifically present in HS lesions and could be reversed by application of IL-1 receptor antagonist. Search for blood parameters associated with IL-1 beta pathway activity in HS identified serum amyloid A, which was synergistically induced by IL-1 beta and IL-6 in hepatocytes. Consequently, strongly elevated blood serum amyloid A levels in HS correlated positively with the extent of inflammatory skin alterations. In summary, the IL-1 beta pathway represents a pathogenetic cascade, whose activity may be therapeutically targeted and monitored by blood SAA levels.