CD147 modulates the differentiation of T-helper 17 cells in patients with rheumatoid arthritis

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• 作者：Hui Yang ; Jian Wang ; Yu Li ; Zhen-Jie Yin ; Ting-Ting Lv ; Ping Zhu and Yan Zhang
• 刊名：APMIS
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：125
• 期：1
• 页码：24-31
• 全文大小：447K
• ISSN：1600-0463

文摘

The role of CD147 in regulation of rheumatoid arthritis (RA) is not fully elucidated. The aim of this study was to investigate the effect of cell-to-cell contact of activated CD14⁺ monocytes with CD4⁺ T cells, and the modulatory role of CD147 on T-helper 17 (Th17) cells differentiation in patients with RA. Twenty confirmed active RA patients and twenty normal controls were enrolled. CD4⁺ T cells and CD14⁺ monocytes were purified by magnetic beads cell sorting. Cells were cultured under different conditions in CD4⁺ T cells alone, direct cell-to-cell contact co-culture of CD4⁺ and CD14⁺ cells, or indirect transwell co-culture of CD4⁺/CD14⁺ cells in response to LPS and anti-CD3 stimulation with or without anti-CD147 antibody pretreatments. The proportion of IL-17-producing CD4⁺ T cells (defined as Th17 cells) was determined by flow cytometry. The levels of interleukin (IL)-17, IL-6, and IL-1β in the supernatants of cultured cells were measured by ELISA. The optimal condition for in vitro induction of Th17 cells differentiation was co-stimulation with 0.1 μg/mL of LPS and 100 ng/mL of anti-CD3 for 3 days under direct cell-to-cell contact co-culture of CD4⁺ and CD14⁺ cells. Anti-CD147 antibody reduced the proportion of Th17 cells, and also inhibited the productions of IL-17, IL-6, and IL-1β in PBMC culture from RA patients. The current results revealed that Th17 differentiation required cell-to-cell contact with activated monocytes. CD147 promoted the differentiation of Th17 cells by regulation of cytokine production, which provided the evidence for pathogenesis and potential therapeutic targets for RA.