Université Paris-Saclay, INSERM UMR1184, Center for Immunology of Viral Infections and Autoimmune Diseases, Le Kremlin Bicêtre, France.
Rheumatology Department, Hôpital Bicêtre, Assistance Publique - Hôpitaux de Paris, Le Kremlin Bicêtre, France.
Front Immunol. 2022 Feb 23;13:832117. doi: 10.3389/fimmu.2022.832117. eCollection 2022.
We previously reported a specific defect of rheumatoid arthritis (RA) monocyte polarization to anti-inflammatory M2-like macrophages related to increased miR-155 expression in all RA patients except those receiving adalimumab (ADA). In this longitudinal study, we examined whether different tumor necrosis factor inhibitors were able to restore monocyte polarization to M2-like macrophages and their effect on the transcriptomic signature.
M2-like polarization induced by human serum AB was studied in 7 healthy donors and 20 RA patients included in the ABIRA cohort before and 3 months after starting ADA or etanercept (ETA). The differential gene expression of M2- and M1-related transcripts was studied in macrophage-derived monocytes after differentiation.
At baseline, RA monocytes showed a defect of polarization to M2-like macrophages as compared with healthy donor monocytes, which was negatively correlated with disease activity. M2-like polarization from circulating monocytes was restored only with ADA and not ETA treatment. The transcriptomic signature demonstrated downregulation of M2-related transcripts and upregulation of M1-related transcripts in active RA. In patients receiving ADA, the transcriptomic signature of M2-related transcripts was restored.
This longitudinal study demonstrates that ADA but not ETA is able to restore the M2-like polarization of monocytes that is defective in RA.
我们之前报道了类风湿关节炎（RA）患者单核细胞向抗炎 M2 样巨噬细胞极化的特定缺陷，这种缺陷与所有 RA 患者（除接受阿达木单抗（ADA）治疗的患者外）miR-155 表达增加有关。在这项纵向研究中，我们研究了不同的肿瘤坏死因子抑制剂是否能够恢复单核细胞向 M2 样巨噬细胞的极化，并研究其对转录组特征的影响。
在 ABIRA 队列中，我们研究了 7 名健康供体和 20 名 RA 患者在开始 ADA 或依那西普（ETA）治疗前和 3 个月后，人血清 AB 诱导的 M2 样极化。在分化后，我们研究了巨噬细胞来源的单核细胞中 M2 和 M1 相关转录物的差异基因表达。
在基线时，与健康供体单核细胞相比，RA 单核细胞向 M2 样巨噬细胞的极化存在缺陷，这种缺陷与疾病活动度呈负相关。只有 ADA 治疗而不是 ETA 治疗才能恢复循环单核细胞的 M2 样极化。转录组特征表明，在活动期 RA 中，M2 相关转录物的表达下调，M1 相关转录物的表达上调。在接受 ADA 治疗的患者中，M2 相关转录物的转录组特征得到恢复。
这项纵向研究表明，ADA 而不是 ETA 能够恢复 RA 中存在缺陷的单核细胞向 M2 样极化。
