Department of Dermatology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan; Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taiwan.
Department of Environmental and Occupational Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan.
J Dermatol Sci. 2018 Sep;91(3):276-284. doi: 10.1016/j.jdermsci.2018.05.009. Epub 2018 May 29.
Psoriasis is a systemic inflammatory disease with dramatic responses to TNF-α inhibitors. TNF-α is mainly produced by macrophages. However, how macrophage polarization contributes to psoriasis remains unknown.
We aimed to investigate the molecular mechanisms of macrophage polarization in psoriasis.
8 patients with moderate to severe psoriasis (Male/Female: 4/4, average age: 47.9 years old) and 8 healthy controls (Male/Female: 4/4, average age: 49.3 years old) were recruited. Their peripheral CD14+ monocytes were isolated with magnetic beads and then were differentiated into macrophages. The differential macrophage polarization was compared among normal controls, psoriatic patients before and after TNF-α inhibitors. The U937 cells were used to investigate the mechanisms by which TNF-α altered the macrophage polarization.
The ratio of M1 to M2a macrophage polarization was higher in psoriatic patients comparing with that in controls. The decreasing M1/M2a ratio was parallel to decreasing PASI severity score after adalimumab treatment. Consistently, TNF-α blockage decreased M1/M2a ratio in U937 cells. The induction of STAT1 and IRF-1 in polarized U937 M1 cells was inhibited by TNF-α inhibitor. However, STAT1 and/or IRF-1 interference could not resume M1 polarization. In skin, the increased M1 and M2 infiltration in lesions returned to baseline after successful treatment with TNF-α inhibitor.
Increased M1 polarization is associated with higher disease severity in psoriasis, resuming to baseline after successful treatment by TNF-α inhibitors. TNF-α blockage inhibits M1 polarization through STAT1- and IRF-1-independent pathways. Macrophage polarization may contribute to disease progression in psoriasis.
银屑病是一种全身性炎症性疾病，对 TNF-α 抑制剂有显著反应。TNF-α 主要由巨噬细胞产生。然而，巨噬细胞极化如何导致银屑病尚不清楚。
我们旨在研究银屑病中巨噬细胞极化的分子机制。
招募 8 名中重度银屑病患者（男/女：4/4，平均年龄：47.9 岁）和 8 名健康对照者（男/女：4/4，平均年龄：49.3 岁）。用磁珠分离他们的外周血 CD14+单核细胞，然后将其分化为巨噬细胞。比较正常对照者、接受 TNF-α 抑制剂治疗前后的银屑病患者之间的差异极化巨噬细胞。使用 U937 细胞研究 TNF-α 改变巨噬细胞极化的机制。
与对照组相比，银屑病患者的 M1 与 M2a 极化的巨噬细胞比值更高。阿达木单抗治疗后，M1/M2a 比值降低与 PASI 严重程度评分降低平行。同样，TNF-α 阻断可降低 U937 细胞中的 M1/M2a 比值。极化的 U937 M1 细胞中 STAT1 和 IRF-1 的诱导被 TNF-α 抑制剂抑制。然而，STAT1 和/或 IRF-1 干扰不能恢复 M1 极化。在皮肤中，成功治疗 TNF-α 抑制剂后，病变处增加的 M1 和 M2 浸润恢复到基线。
银屑病中 M1 极化增加与疾病严重程度相关，成功治疗 TNF-α 抑制剂后恢复到基线。TNF-α 阻断通过 STAT1-和 IRF-1 非依赖性途径抑制 M1 极化。巨噬细胞极化可能有助于银屑病的疾病进展。
