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痤疮丙酸杆菌相关健康皮肤和痤疮皮肤分离株诱导的 Th17 细胞表型和抗菌活性。

Phenotype and Antimicrobial Activity of Th17 Cells Induced by Propionibacterium acnes Strains Associated with Healthy and Acne Skin.

机构信息

Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

Division of Dermatology, David Geffen School of Medicine at UCLA, Los Angeles, California, USA.

出版信息

J Invest Dermatol. 2018 Feb;138(2):316-324. doi: 10.1016/j.jid.2017.07.842. Epub 2017 Aug 31.

Abstract

Studies of the human skin microbiome suggest that Propionibacterium acnes strains may contribute differently to skin health and disease. However, the immune phenotype and functions of T helper type 17 (Th17) cells induced by healthy (P) versus acne (P) skin-associated P. acnes strains are currently unknown. We stimulated peripheral blood mononuclear cells from healthy donors and observed that P strains induce higher IL-17 levels than P strains. We next generated P and P strain-specific Th17 clones and show that P. acnes strains induce Th17 cells of varied phenotype and function that are stable in the presence of IL-2 and IL-23. Although P- and P-specific clones expressed similar levels of LL-37 and DEFB4, only P-specific clones secreted molecules sufficient to kill P. acnes. Furthermore, electron microscopic studies showed that supernatants derived from activated P and not P-specific clones exhibited robust bactericidal activity against P. acnes, and complete breaches in the bacterial cell envelope were observed. This antimicrobial activity was independent of IL-26, because both natural IL-26 released by Th17 clones and rhIL-26 lacked antimicrobial potency against P. acnes. Overall, our data suggest that P. acnes strains may differentially modulate the CD4 T-cell responses, leading to the generation of Th17 cells that may contribute to either homeostasis or acne pathogenesis.

摘要

对人类皮肤微生物组的研究表明,痤疮丙酸杆菌(Propionibacterium acnes)菌株可能对皮肤健康和疾病有不同的影响。然而,目前尚不清楚健康(P)和痤疮(P)相关的 P. acnes 菌株诱导的辅助性 T 细胞 17(Th17)细胞的免疫表型和功能。我们刺激健康供体的外周血单核细胞,发现 P 菌株诱导的 IL-17 水平高于 P 菌株。接下来,我们生成了 P 和 P 菌株特异性 Th17 克隆,并表明 P. acnes 菌株诱导的 Th17 细胞具有不同的表型和功能,在 IL-2 和 IL-23 的存在下稳定。尽管 P-和 P-特异性克隆表达相似水平的 LL-37 和 DEFB4,但只有 P-特异性克隆分泌的分子足以杀死 P. acnes。此外,电子显微镜研究表明,来自激活的 P 而非 P-特异性克隆的上清液对 P. acnes 表现出强大的杀菌活性,并且观察到细菌细胞包膜的完全破裂。这种抗菌活性与 IL-26 无关,因为 Th17 克隆释放的天然 IL-26 和 rhIL-26 均对 P. acnes 缺乏抗菌效力。总体而言,我们的数据表明,P. acnes 菌株可能会差异调节 CD4 T 细胞反应,导致产生可能有助于稳态或痤疮发病机制的 Th17 细胞。

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