GITR/GITRL interaction promotes the expansion of T helper 9 and T helper 17 in psoriatic arthritis.

IF 3.4 4区 医学 Q2 RHEUMATOLOGY
Lidia La Barbera, Chiara Rizzo, Marianna Lo Pizzo, Diana Di Liberto, Marco Pio La Manna, Leila Mohammadnezhad, Federica Camarda, Guido Sireci, Francesco Ciccia, Giuliana Guggino
{"title":"GITR/GITRL interaction promotes the expansion of T helper 9 and T helper 17 in psoriatic arthritis.","authors":"Lidia La Barbera, Chiara Rizzo, Marianna Lo Pizzo, Diana Di Liberto, Marco Pio La Manna, Leila Mohammadnezhad, Federica Camarda, Guido Sireci, Francesco Ciccia, Giuliana Guggino","doi":"10.55563/clinexprheumatol/31hjvf","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by the involvement of multiple targets. Accumulating evidence suggests the key role played by T helper (Th)9 and Th17 cells in PsA. Recently, the ability to activate GITR in promoting differentiation and proliferation of Th17 and Th9 cells has been investigated in several inflammatory conditions. We aimed to evaluate the effects of GITR/GITRL interaction in the immune responses underlying the disease, including the main PsA target sites.</p><p><strong>Methods: </strong>Twenty-one PsA patients with active disease, naive to disease-modifying anti-rheumatic drugs, were enrolled. Peripheral blood mononuclear cells and synovial fluid (SF) mononuclear cells were collected to assess GITR and GITRL expression by flow cytometry. An in vitro functional assay with recombinant GITR agonist was performed to detect the effect on T cell subsets. Synovial and ileal biopsies were obtained to evaluate GITR and GITRL expression by immunofluorescence. Healthy subjects and osteoarthritis patients were enrolled as controls.</p><p><strong>Results: </strong>We reported an increased in vitro expression of GITR among CD4+ T cells and its cognate ligand GITRL on antigen-presenting cells in PsA peripheral blood. In vitro, the addition of the GITR agonist resulted in increased expansion of Th9 and Th17 cells. Increased expression of GITR and GITRL was found even in PsA SF, synovium and ileum.</p><p><strong>Conclusions: </strong>Our results suggest a novel role of GITR/GITRL in promoting the expansion of Th9 and Th17 in PsA-inflamed tissues.</p>","PeriodicalId":10274,"journal":{"name":"Clinical and experimental rheumatology","volume":" ","pages":""},"PeriodicalIF":3.4000,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and experimental rheumatology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.55563/clinexprheumatol/31hjvf","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"RHEUMATOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory disease characterised by the involvement of multiple targets. Accumulating evidence suggests the key role played by T helper (Th)9 and Th17 cells in PsA. Recently, the ability to activate GITR in promoting differentiation and proliferation of Th17 and Th9 cells has been investigated in several inflammatory conditions. We aimed to evaluate the effects of GITR/GITRL interaction in the immune responses underlying the disease, including the main PsA target sites.

Methods: Twenty-one PsA patients with active disease, naive to disease-modifying anti-rheumatic drugs, were enrolled. Peripheral blood mononuclear cells and synovial fluid (SF) mononuclear cells were collected to assess GITR and GITRL expression by flow cytometry. An in vitro functional assay with recombinant GITR agonist was performed to detect the effect on T cell subsets. Synovial and ileal biopsies were obtained to evaluate GITR and GITRL expression by immunofluorescence. Healthy subjects and osteoarthritis patients were enrolled as controls.

Results: We reported an increased in vitro expression of GITR among CD4+ T cells and its cognate ligand GITRL on antigen-presenting cells in PsA peripheral blood. In vitro, the addition of the GITR agonist resulted in increased expansion of Th9 and Th17 cells. Increased expression of GITR and GITRL was found even in PsA SF, synovium and ileum.

Conclusions: Our results suggest a novel role of GITR/GITRL in promoting the expansion of Th9 and Th17 in PsA-inflamed tissues.

GITR/GITRL相互作用促进银屑病关节炎中辅助性T 9和辅助性T 17的扩增。
目的:银屑病关节炎(PsA)是一种以多靶点参与为特征的慢性炎症性疾病。越来越多的证据表明辅助性T (Th)9和Th17细胞在PsA中起关键作用。最近,在几种炎症条件下,已经研究了激活GITR促进Th17和Th9细胞分化和增殖的能力。我们的目的是评估GITR/GITRL相互作用在潜在疾病的免疫反应中的作用,包括主要的PsA靶点。方法:纳入21例活动性PsA患者,首次使用抗风湿药物。采集外周血单个核细胞和滑液(SF)单个核细胞,流式细胞术检测GITR和GITRL的表达。用重组GITR激动剂进行体外功能测定,检测其对T细胞亚群的影响。行滑膜和回肠活检,免疫荧光法检测GITR和GITRL的表达。健康受试者和骨关节炎患者作为对照。结果:我们报道了CD4+ T细胞中GITR及其同源配体GITRL在PsA外周血抗原呈递细胞中的体外表达增加。在体外,GITR激动剂的加入导致Th9和Th17细胞的扩增增加。GITR和GITRL的表达在PsA SF、滑膜和回肠中均有升高。结论:我们的研究结果提示GITR/GITRL在促进psa炎症组织中Th9和Th17扩增中的新作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
6.10
自引率
18.90%
发文量
377
审稿时长
3-6 weeks
期刊介绍: Clinical and Experimental Rheumatology is a bi-monthly international peer-reviewed journal which has been covering all clinical, experimental and translational aspects of musculoskeletal, arthritic and connective tissue diseases since 1983.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信