Kelhälä Hanna-Leena, Palatsi Riitta, Fyhrquist Nanna, Lehtimäki Sari, Väyrynen Juha P, Kallioinen Matti, Kubin Minna E, Greco Dario, Tasanen Kaisa, Alenius Harri, Bertino Beatrice, Carlavan Isabelle, Mehul Bruno, Déret Sophie, Reiniche Pascale, Martel Philippe, Marty Carine, Blume-Peytavi Ulrike, Voegel Johannes J, Lauerma Antti
Department of Dermatology, University of Oulu and Medical Research Center, Oulu University Hospital, Oulu, Finland.
Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland.
PLoS One. 2014 Aug 25;9(8):e105238. doi: 10.1371/journal.pone.0105238. eCollection 2014.
The mechanisms of inflammation in acne are currently subject of intense investigation. This study focused on the activation of adaptive and innate immunity in clinically early visible inflamed acne lesions and was performed in two independent patient populations. Biopsies were collected from lesional and non-lesional skin of acne patients. Using Affymetrix Genechips, we observed significant elevation of the signature cytokines of the Th17 lineage in acne lesions compared to non-lesional skin. The increased expression of IL-17 was confirmed at the RNA and also protein level with real-time PCR (RT-PCR) and Luminex technology. Cytokines involved in Th17 lineage differentiation (IL-1β, IL-6, TGF-β, IL23p19) were remarkably induced at the RNA level. In addition, proinflammatory cytokines and chemokines (TNF-α, IL-8, CSF2 and CCL20), Th1 markers (IL12p40, CXCR3, T-bet, IFN-γ), T regulatory cell markers (Foxp3, IL-10, TGF-β) and IL-17 related antimicrobial peptides (S100A7, S100A9, lipocalin, hBD2, hBD3, hCAP18) were induced. Importantly, immunohistochemistry revealed significantly increased numbers of IL-17A positive T cells and CD83 dendritic cells in the acne lesions. In summary our results demonstrate the presence of IL-17A positive T cells and the activation of Th17-related cytokines in acne lesions, indicating that the Th17 pathway is activated and may play a pivotal role in the disease process, possibly offering new targets of therapy.
痤疮炎症机制目前是深入研究的课题。本研究聚焦于临床早期可见的炎性痤疮皮损中适应性免疫和固有免疫的激活,并在两个独立的患者群体中进行。从痤疮患者的皮损和非皮损皮肤处采集活检样本。使用Affymetrix基因芯片,我们观察到与非皮损皮肤相比,痤疮皮损中Th17谱系的标志性细胞因子显著升高。通过实时PCR(RT-PCR)和Luminex技术在RNA及蛋白水平证实了IL-17表达增加。参与Th17谱系分化的细胞因子(IL-1β、IL-6、TGF-β、IL23p19)在RNA水平显著上调。此外,促炎细胞因子和趋化因子(TNF-α、IL-8、CSF2和CCL20)、Th1标志物(IL12p40、CXCR3、T-bet、IFN-γ)、调节性T细胞标志物(Foxp3、IL-10、TGF-β)以及IL-17相关抗菌肽(S100A7、S100A9、脂钙蛋白、hBD2、hBD3、hCAP18)均被诱导表达。重要的是,免疫组化显示痤疮皮损中IL-17A阳性T细胞和CD83树突状细胞数量显著增加。总之,我们的结果表明痤疮皮损中存在IL-17A阳性T细胞且Th17相关细胞因子被激活,提示Th17通路被激活并可能在疾病进程中起关键作用,这可能为治疗提供新靶点。