Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan.
Department of Dermatology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan; Department of Bacteriology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Japan.
J Dermatol Sci. 2017 Dec;88(3):271-279. doi: 10.1016/j.jdermsci.2017.08.001. Epub 2017 Aug 5.
Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The skin of patients with AD presents as a disbalance of the microbiome with a strong colonization by Staphylococcus aureus, which positively correlates with the severity of the disease. However, the effect of colonized S. aureus on the skin immune system has not been fully elucidated.
The aim of this study is to explore whether S. aureus isolated from AD skin is able to skew T cell responses via Langerhans cells (LC) as compared to a standard strain of S. aureus and S. epidermidis.
We prepared monocyte-derived LC (MoLC) from healthy controls and patients with AD, and stimulated MoLC with a standard strain of S. aureus NCTC8325, S. aureus TF3378 isolated from AD skin, or S. epidermidis. Stimulated MoLC were co-cultured with autologous CD4 T cells and then T cell responses were analyzed by T cell polarization assays, cytokine analysis and real-time PCR.
MoLC stimulated by S. aureus TF3378 induced significantly high and rapid proliferation of T cells as compared to those by S. aureus NCTC8325 and S. epidermidis. Cytokine productions from T cells cultured with S. aureus TF3378-stimulated MoLC showed significantly high amounts of IL-2 and less IFN-γ production with imbalanced Th1/Th2 (decreased TBX21/GATA3 ratio) mRNA expression. The T cell proliferation with increased IL-2 production via S. aureus TF3378-stimulated MoLC was diminished by treatment of proteinase K.
S. aureus TF3378 on AD skin can skew T cell responses via LC toward imbalanced Th1/Th2 skin immunity.
特应性皮炎(AD)是最常见的慢性炎症性皮肤病之一。AD 患者的皮肤微生物组失衡,金黄色葡萄球菌(S. aureus)大量定植,且其定植程度与疾病严重程度呈正相关。然而,定植的 S. aureus 对皮肤免疫系统的影响尚未完全阐明。
本研究旨在探索 AD 皮肤分离的 S. aureus 是否能够通过朗格汉斯细胞(LC)使 T 细胞反应发生偏移,与标准 S. aureus 株和表皮葡萄球菌(S. epidermidis)相比。
我们从健康对照者和 AD 患者中制备单核细胞来源的 LC(MoLC),并用标准 S. aureus NCTC8325、AD 皮肤分离的 S. aureus TF3378 或 S. epidermidis 刺激 MoLC。刺激后的 MoLC 与自体 CD4 T 细胞共培养,然后通过 T 细胞极化测定、细胞因子分析和实时 PCR 分析 T 细胞反应。
与 S. aureus NCTC8325 和 S. epidermidis 相比,S. aureus TF3378 刺激的 MoLC 可显著诱导 T 细胞快速而高的增殖。与用 S. aureus TF3378 刺激的 MoLC 共培养的 T 细胞产生的细胞因子显示出显著高量的 IL-2 和较少的 IFN-γ产生,伴有 Th1/Th2 (TBX21/GATA3 比值降低)mRNA 表达失衡。用蛋白酶 K 处理后,通过 S. aureus TF3378 刺激的 MoLC 增加的 IL-2 产生所导致的 T 细胞增殖减少。
AD 皮肤上的 S. aureus TF3378 可通过 LC 使 T 细胞反应向不平衡的 Th1/Th2 皮肤免疫倾斜。