Université Paris-Sud, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, 94270 Le Kremlin Bicêtre, France;
Université Paris-Sud, INSERM U1184, Center for Immunology of Viral Infections and Autoimmune Diseases, 94270 Le Kremlin Bicêtre, France.
J Immunol. 2019 Oct 1;203(7):1766-1775. doi: 10.4049/jimmunol.1900386. Epub 2019 Sep 4.
Proinflammatory macrophages and miR-155 are increased in patients with rheumatoid arthritis (RA). We studied membrane TNF (mTNF) expression on blood monocytes, polarization into macrophages, miR-155 expression, and the effect of anti-TNF on these biomarkers in RA patients. Sixty-seven RA patients and 109 controls (55 healthy, 54 with spondyloarthritis and connective tissue diseases) were studied. Monocytes were isolated and differentiated into macrophages with or without anti-TNF. mTNF expression was increased on monocytes from RA patients, but not from other inflammatory diseases, correlated with disease activity. Under human serum AB or M-CSF, only monocytes from RA had a defect of differentiation into M2-like macrophages and had a propensity for preferential maturation toward M1-like macrophages that contributed to synovial inflammation. This defect was correlated to mTNF expression and was partially reversed by monoclonal anti-TNF Abs but not by the TNF soluble receptor. miR-155 was increased in M2-macrophages except in adalimumab-treated patients. Transfection of healthy monocytes with miR-155 induced a decrease in M2-like markers, and transfection of RA monocytes with antagomir-155 allowed restoration of M2-like polarization. Defect in differentiation of monocytes into M2-like-macrophages linked to increased miR-155 and correlated with increased mTNF on monocytes could play a key role in RA pathogenesis. Monoclonal anti-TNF Abs but not the TNF soluble receptor partially restored this defect.
促炎巨噬细胞和 miR-155 在类风湿关节炎（RA）患者中增加。我们研究了血液单核细胞上的膜 TNF（mTNF）表达、向巨噬细胞的极化、miR-155 表达以及抗 TNF 对 RA 患者这些生物标志物的影响。研究了 67 名 RA 患者和 109 名对照者（55 名健康者，54 名脊柱关节炎和结缔组织疾病患者）。分离单核细胞并在有或没有抗 TNF 的情况下分化为巨噬细胞。RA 患者的单核细胞 mTNF 表达增加，但其他炎症性疾病患者的单核细胞没有增加，且与疾病活动度相关。在人血清 AB 或 M-CSF 下，只有 RA 患者的单核细胞分化为 M2 样巨噬细胞存在缺陷，并且倾向于优先向促进滑膜炎症的 M1 样巨噬细胞成熟。这种缺陷与 mTNF 表达相关，并且可部分被单克隆抗 TNF Abs 但不是 TNF 可溶性受体逆转。M2 样巨噬细胞中 miR-155 增加，但在阿达木单抗治疗的患者中除外。健康单核细胞转染 miR-155 会诱导 M2 样标志物减少，而 RA 单核细胞转染 antagomir-155 则可恢复 M2 样极化。与单核细胞上 mTNF 增加相关的单核细胞向 M2 样巨噬细胞分化缺陷可能在 RA 发病机制中起关键作用。单克隆抗 TNF Abs 但不是 TNF 可溶性受体可部分恢复这种缺陷。
