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