Department of Pharmacology, Institute of Post Graduate Medical Education and Research, Kolkata, India.
Rheumatology and Clinical Immunology, Institute of Post Graduate Medical Education and Research, Kolkata, India.
Free Radic Res. 2022 Mar-Apr;56(3-4):290-302. doi: 10.1080/10715762.2022.2089567. Epub 2022 Jun 22.
Rheumatoid arthritis (RA) is an autoimmune disorder whose etiopathology involves an interplay between genetic and environmental factors, with oxidative stress being a key contributory factor. This study aimed to establish the impact, if any, of an oxidative, pro-inflammatory milieu upon trans-differentiation of neutrophils and disease progression. In the synovial fluid (SF) and peripheral blood sourced from patients with RA ( = 40) along with healthy controls ( = 25), the proportion of neutrophil-dendritic (N-DC) cell hybrids, i.e. CD66b/CD83 was characterized in terms of their antigen presentation (HLA-DR, CD80, andCD86) and cell adhesion and migration (ICAM-1, VCAM-1, and CD62L) properties, along with their ability to generate reactive oxygen species (ROS). In the SF of RA cases, the raised levels of circulating and intra-neutrophilic pro-inflammatory cytokines/chemokines were accompanied by an enhanced proportion of CD66b neutrophils, that co-expressed features of antigen presenting cells (APCs) namely CD83, HLA-DR, CD80, CD86, ICAM-1, VCAM-1, and decreased CD62L. These N-DCs as compared to canonical neutrophils demonstrated a higher generation of ROS, and their frequency positively correlated with disease activity score (DAS28). An functional assay validated that oxidative stress supported trans-differentiation and could be attenuated by a free radical scavenger. Taken together, the pro-inflammatory microenvironment in the SF of patients with RA coupled with a higher generation of ROS promoted the trans-differentiation of neutrophils into N-DCs, suggesting the inclusion of anti-oxidants as an add-on therapeutic strategy to limit trans-differentiation.
类风湿关节炎（RA）是一种自身免疫性疾病，其发病机制涉及遗传和环境因素的相互作用，氧化应激是一个关键的促成因素。本研究旨在确定氧化、促炎环境对中性粒细胞的转分化及其疾病进展的影响。在 RA 患者的滑液（SF）和外周血（n = 40）以及健康对照者（n = 25）中，特征在于其抗原呈递（HLA-DR、CD80 和 CD86）和细胞黏附和迁移（ICAM-1、VCAM-1 和 CD62L）特性，以及其产生活性氧物种（ROS）的能力。在 RA 患者的 SF 中，循环和细胞内促炎细胞因子/趋化因子水平升高，同时伴有 CD66b 中性粒细胞比例增加，这些细胞表达抗原呈递细胞（APC）的特征，即 CD83、HLA-DR、CD80、CD86、ICAM-1、VCAM-1 和 CD62L 减少。与经典中性粒细胞相比，这些 N-DC 产生 ROS 的能力更高，其频率与疾病活动评分（DAS28）呈正相关。功能测定验证了氧化应激支持转分化，并且可以通过自由基清除剂来减弱。总之，RA 患者 SF 中的促炎微环境加上更高的 ROS 生成促进了中性粒细胞向 N-DC 的转分化，表明抗氧化剂的加入是一种附加的治疗策略，以限制转分化。
