B-cell depletion therapy reduces retinal inflammation in experimental autoimmune uveoretinitis

IF 4.7 2区医学 Q2 IMMUNOLOGY

International immunopharmacology Pub Date : 2025-03-20 DOI:10.1016/j.intimp.2025.114467

Zhiruo Wang , Gong Chen , Cong Zhao , Yunping Li , Jingming Shi , Huihui Chen , Guochun Chen

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引用次数: 0

Abstract

Objective: Non-infectious uveitis (NIU) is recognized as a group of autoimmune sight-threatening disorders with complex pathogenesis. This study aims to analyze the pathogenic role of B cells in NIU and evaluate the effectiveness of B cell depletion therapy in experimental autoimmune uveoretinitis (EAU) mice.

Methods: We performed high throughput transcriptome sequence on peripheral blood samples from healthy individuals (n = 6) and NIU patients (n = 12), and reanalyzed single-cell RNA transcriptome data of aqueous humor in NIU patients (n = 5). Female C57BL/6 J mice were induced the EAU model through immunization with the IRBP₆₅₁_–₆₇₀ peptide. B cell depletion was performed via intravitreal injection of anti-CD20 antibody on day 7 and mice were executed on day 14 following antigen administration. Clinical symptoms were assessed by fundus photography and fundus fluorescein angiography. Pathological sections were analyzed using immunohistochemistry and immunofluorescence. Serum immunoglobulins and inflammatory factors were detected by ELISA.

Results: Transcriptome sequencing and single-cell RNA analysis revealed strong B cell immune responses in both peripheral blood and aqueous humor of NIU patients. Intravitreal injection of anti-CD20 antibody partially reduces B cell numbers, suppresses T cell proliferation in CLNs, and decreases serum IgG and inflammatory cytokines level, which collectively alleviate clinical symptoms and mitigate retinal inflammation. Significant differences in BCR sequences were observed between the NIU groups and healthy controls.

Conclusion: B-cell depletion therapy may offer a novel strategy for the treatment of NIU and identifying specific BCR sequences provides a potential target for both therapeutic intervention and disease monitoring.

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b细胞耗竭疗法可减少实验性自身免疫性葡萄膜视网膜炎的视网膜炎症。

目的：非感染性葡萄膜炎（non -传染性葡萄膜炎，NIU）是一种发病机制复杂的自身免疫性视力疾病。本研究旨在分析B细胞在实验性自身免疫性葡萄膜视网膜炎（EAU）小鼠中的致病作用，并评价B细胞耗竭治疗的有效性。方法：对健康个体（n = 6）和NIU患者（n = 12）外周血样本进行高通量转录组测序，并对NIU患者（n = 5）房水单细胞RNA转录组数据进行再分析。用IRBP651-670肽免疫雌性C57BL/6 J小鼠诱导EAU模型。第7天玻璃体内注射抗cd20抗体去B细胞，第14天处死小鼠。通过眼底摄影和眼底荧光素血管造影评估临床症状。病理切片采用免疫组织化学和免疫荧光分析。ELISA法检测血清免疫球蛋白和炎性因子。结果：转录组测序和单细胞RNA分析显示，牛牛患者外周血和房水均有较强的B细胞免疫应答。玻璃体内注射抗cd20抗体部分减少B细胞数量，抑制cln内T细胞增殖，降低血清IgG和炎性细胞因子水平，共同缓解临床症状，减轻视网膜炎症。在牛组和健康对照组之间观察到BCR序列的显著差异。结论：b细胞耗竭疗法可能为治疗牛牛提供一种新的策略，鉴定特异性BCR序列为治疗干预和疾病监测提供了潜在的靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International immunopharmacology 医学-免疫学

CiteScore

8.40

自引率

3.60%

发文量

935

审稿时长

53 days

期刊介绍： International Immunopharmacology is the primary vehicle for the publication of original research papers pertinent to the overlapping areas of immunology, pharmacology, cytokine biology, immunotherapy, immunopathology and immunotoxicology. Review articles that encompass these subjects are also welcome. The subject material appropriate for submission includes: • Clinical studies employing immunotherapy of any type including the use of: bacterial and chemical agents; thymic hormones, interferon, lymphokines, etc., in transplantation and diseases such as cancer, immunodeficiency, chronic infection and allergic, inflammatory or autoimmune disorders. • Studies on the mechanisms of action of these agents for specific parameters of immune competence as well as the overall clinical state. • Pre-clinical animal studies and in vitro studies on mechanisms of action with immunopotentiators, immunomodulators, immunoadjuvants and other pharmacological agents active on cells participating in immune or allergic responses. • Pharmacological compounds, microbial products and toxicological agents that affect the lymphoid system, and their mechanisms of action. • Agents that activate genes or modify transcription and translation within the immune response. • Substances activated, generated, or released through immunologic or related pathways that are pharmacologically active. • Production, function and regulation of cytokines and their receptors. • Classical pharmacological studies on the effects of chemokines and bioactive factors released during immunological reactions.