Quercetin ameliorates lupus symptoms by promoting the apoptosis of senescent Tfh cells via the Bcl-2 pathway.

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Immunity & Ageing Pub Date : 2024-10-15 DOI:10.1186/s12979-024-00474-9
Feng Xiong, Kai Shen, Di Long, Suqing Zhou, Pinglang Ruan, Yue Xin, Yuezheng Xiao, Weijun Peng, Ming Yang, Haijing Wu, Qianjin Lu
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Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disorder that commonly affects the skin, kidneys, joints, and various other systemic tissues, with its development intricately linked to the process of immunosenescence. Quercetin (QC), a phytochemical that occurs naturally, demonstrates many different biological capabilities, such as antibacterial, antioxidant, and anti-inflammatory activities. Our investigation found that QC effectively reduced kidney damage and relieved mesenteric lymph nodes (mLNs) swelling in MRL/lpr lupus mice. Moreover, QC has been found to decrease the number of senescent follicular helper T (Tfh) cells, a pivotal kind of T cells that contribute to the progression of SLE. In vitro, QC exhibited the capacity to modulate mRNA expression levels, with the downregulation of IL-6, IL21-AS1, IL-27, BCL6, and BCL2L12, and the upregulation of FOXP1 and BIM. This modulation resulted in the suppression of Tfh cells differentiation and the enhancement of apoptosis in senescent CD4+ T cells. In addition, the HuProtTM Human Proteome Microarray revealed that QC can directly bind to BCL-2 protein and therefore promote the apoptosis of senescent CD4+ T cell. As a result, our investigative elucidate the potent inhibitory action of QC on the ontogeny of Tfh cells, along with its capacity to abrogate the immunosenescent phenotype. This positions QC as a promising therapeutic strategy for treating SLE.

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槲皮素通过 Bcl-2 途径促进衰老的 Tfh 细胞凋亡,从而改善狼疮症状。
系统性红斑狼疮(SLE)是一种自身免疫性疾病,通常会影响皮肤、肾脏、关节和其他各种系统组织,其发病与免疫衰老过程密切相关。槲皮素(QC)是一种天然存在的植物化学物质,具有抗菌、抗氧化和抗炎等多种生物学功能。我们的研究发现,QC 能有效减轻 MRL/lpr 狼疮小鼠的肾脏损伤,缓解肠系膜淋巴结肿大。此外,我们还发现 QC 能减少衰老的滤泡辅助性 T 细胞(Tfh)的数量。在体外,QC 有能力调节 mRNA 表达水平,下调 IL-6、IL21-AS1、IL-27、BCL6 和 BCL2L12,上调 FOXP1 和 BIM。这种调节抑制了 Tfh 细胞的分化,并增强了衰老 CD4+ T 细胞的凋亡。此外,HuProtTM 人类蛋白质组芯片显示,QC 可直接与 BCL-2 蛋白结合,从而促进衰老的 CD4+ T 细胞凋亡。因此,我们的研究阐明了 QC 对 Tfh 细胞发育的强效抑制作用,以及其消除免疫衰老表型的能力。这使 QC 成为治疗系统性红斑狼疮的一种有前途的治疗策略。
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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
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