Department of Clinical Laboratory, First Affiliated Hospital of Nanchang University, Nanchang, China.
Department of Medical College, Nanchang University, Nanchang, China.
J Immunotoxicol. 2022 Dec;19(1):53-60. doi: 10.1080/1547691X.2022.2067916.
As an important m6A reader, the YT521-B homology domain family 2 (YTHDF2) has been shown to regulate mRNA degradation and translation, and to be involved in inflammation. However, little is known about the role of YTHDF2 in the autoimmune-based inflammatory disease rheumatoid arthritis (RA). To begin to ascertain any role for this reader, 74 RA patients and 63 healthy controls (HC) were recruited for this study. Blood was collected from each subject and peripheral blood mononuclear cells (PBMC) isolated. Thereafter, mRNA expression of , interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor (TNF)-α in the cells was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The harvested blood was also assessed for a variety of parameters, including levels of C-reactive protein (CRP), erythrocyte sedimentation rates (ESR), white blood cell counts (WBC), neutrophils counts (N)/neutrophils percentages (N%), and neutrophil:lymphocyte ratios (NLR) - each markers of inflammation during RA. The results showed that mRNA expression in RA patient PBMC was decreased significantly vs that in healthy control subject cells. Further, mRNA expression in RA patient PBMC negatively-correlated with ESR, CRP levels, WBC counts, as well as neutrophils counts, percentages, and NLR values. In addition, it was seen that mRNA expression in RA patient PBMC was associated with host serum RF levels and treatment. Moreover, it was found that mRNA expression of IL-1β, IL-6, IL-8, and TNFα was increased in PBMC from RA patients relative to in control subject cells; however, only the increased IL-1β expression was seen to be negatively-correlated with decreased mRNA expression. In conclusion, the present study illustrated that expression might have some regulatory role in the underlying mechanisms associated with the autoimmune disease RA and that this m6A reader could at some point represent a potential target for regulating inflammatory responses that occur during RA.
作为一种重要的 m6A 读码器，Y 类包含 T 521-B 结构域家族 2（YTHDF2）已被证明可以调节 mRNA 降解和翻译，并参与炎症反应。然而，关于 YTHDF2 在自身免疫性炎症性疾病类风湿关节炎（RA）中的作用知之甚少。为了开始确定这种读码器的任何作用，本研究招募了 74 名 RA 患者和 63 名健康对照者（HC）。从每个受试者采集血液并分离外周血单核细胞（PBMC）。然后，通过定量逆转录-聚合酶链反应（qRT-PCR）测定细胞中 的 mRNA 表达、白细胞介素（IL）-1β、IL-6、IL-8 和肿瘤坏死因子（TNF）-α。还评估了采集的血液的各种参数，包括 C 反应蛋白（CRP）水平、红细胞沉降率（ESR）、白细胞计数（WBC）、中性粒细胞计数（N）/中性粒细胞百分比（N%）和中性粒细胞：淋巴细胞比值（NLR）-这些都是 RA 期间炎症的标志物。结果表明，与健康对照组细胞相比，RA 患者 PBMC 中的 mRNA 表达显著降低。此外，RA 患者 PBMC 中的 mRNA 表达与 ESR、CRP 水平、WBC 计数以及中性粒细胞计数、百分比和 NLR 值呈负相关。此外，还发现 RA 患者 PBMC 中的 mRNA 表达与宿主血清 RF 水平和治疗有关。此外，发现 RA 患者 PBMC 中 IL-1β、IL-6、IL-8 和 TNFα 的 mRNA 表达增加，而对照细胞中则相对增加；然而，只有增加的 IL-1β 表达与降低的 mRNA 表达呈负相关。综上所述，本研究表明 表达可能在与自身免疫性疾病 RA 相关的潜在机制中具有一些调节作用，并且这种 m6A 读码器在某种程度上可能代表调节 RA 期间发生的炎症反应的潜在靶标。
