Engaging PD-1 rescues regulatory T cell function and inhibits inflammatory T cells in rheumatoid arthritis.

IF 3.4 3区 医学 Q3 IMMUNOLOGY
Kaustav Chowdhury, Uma Kumar, Jaydeep Chaudhuri, Prabin Kumar, Soumabha Das, Maumita Kanjilal, Parasar Ghosh, Ravi Kiran Basyal, Uma Kanga, Santu Bandyopadhaya, Dipendra Kumar Mitra
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引用次数: 0

Abstract

Background: Despite their synovial enrichment Regulatory T cells (Treg) fail to alleviate the joint inflammation in rheumatoid arthritis (RA). This indicates their functional impairment in the synovial milieu of RA patients.

Results: Here, we demonstrate that deficit in PD-1 pathway incapacitates the synovial Treg cells and engaging PD-1 restores their suppressive function (IL-10, TGF-β secretion) which in turn suppressed the synovial inflammatory T cells (IFN-γ+, IL-17+ TNF-α+). We also showed deficit in programmed death ligand-1 (PD-L1) expression on RA synovial macrophages contributes to impaired Treg cell function.

Conclusion: Rejuvenating synovial Treg cell function via PD-1 engagement may be a potential strategy to ameliorate the synovial inflammation in RA patients.

参与PD-1拯救类风湿关节炎的调节性T细胞功能并抑制炎性T细胞。
背景:尽管滑膜富集调节性T细胞(Treg)不能缓解类风湿性关节炎(RA)的关节炎症。这表明它们在RA患者滑膜环境中的功能损害。结果:在这里,我们证明了PD-1通路的缺陷使滑膜Treg细胞丧失能力,参与PD-1恢复其抑制功能(IL-10, TGF-β分泌),从而抑制滑膜炎症T细胞(IFN-γ+, IL-17+ TNF-α+)。我们还发现RA滑膜巨噬细胞的程序性死亡配体-1 (PD-L1)表达缺陷导致Treg细胞功能受损。结论:通过PD-1参与恢复滑膜Treg细胞功能可能是改善RA患者滑膜炎症的潜在策略。
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来源期刊
CiteScore
8.40
自引率
2.20%
发文量
101
审稿时长
3-8 weeks
期刊介绍: Clinical & Experimental Immunology (established in 1966) is an authoritative international journal publishing high-quality research studies in translational and clinical immunology that have the potential to transform our understanding of the immunopathology of human disease and/or change clinical practice. The journal is focused on translational and clinical immunology and is among the foremost journals in this field, attracting high-quality papers from across the world. Translation is viewed as a process of applying ideas, insights and discoveries generated through scientific studies to the treatment, prevention or diagnosis of human disease. Clinical immunology has evolved as a field to encompass the application of state-of-the-art technologies such as next-generation sequencing, metagenomics and high-dimensional phenotyping to understand mechanisms that govern the outcomes of clinical trials.
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