{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T02:01:57Z","timestamp":1789610517138,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,9,16]],"date-time":"2024-09-16T00:00:00Z","timestamp":1726444800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2021JDRC0045"],"award-info":[{"award-number":["2021JDRC0045"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["2021YFS0164"],"award-info":[{"award-number":["2021YFS0164"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012542","name":"Sichuan Province Science and Technology Support Program","doi-asserted-by":"publisher","award":["24ZDYF0224"],"award-info":[{"award-number":["24ZDYF0224"]}],"id":[{"id":"10.13039\/100012542","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2024,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n Idiopathic inflammatory myopathy (IIM) is a systemic autoimmune disease characterized by skeletal muscle involvement. This study aimed to investigate the role of adenosine receptor signalling pathways in the development of experimental autoimmune myositis (EAM).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n An ecto\u20105\u2032\u2010nucleotidase (CD73) inhibitor, adenosine receptor agonists, a hypoxia\u2010inducible factor\u20101\u03b1 (HIF\u20101\u03b1) inhibitor or a vehicle were administered to control and EAM mice. Murine splenic CD4\n +<\/jats:sup>\n or regulatory T cells (Tregs) were isolated using magnetic beads and subsequently stimulated with an adenosine A2B receptor agonist, a HIF\u20101\u03b1 inhibitor, or vehicle in vitro. In cross\u2010sectional studies, we collected 64 serum samples (69% female, 49\u00a0\u00b1\u00a09\u00a0years), 63 peripheral blood samples (70% female, 50\u00a0\u00b1\u00a011\u00a0years), and 34 skeletal muscle samples (71% female, 63\u00a0\u00b1\u00a06\u00a0years) from patients with IIM. Additionally, 35 serum samples and 30 peripheral blood samples were obtained from age\u2010 and sex\u2010matched healthy controls, and six quadriceps muscle samples were collected from patients with osteoarthritis to serve as the normal group.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Patients with IIM exhibited increased CD73 [dermatomyositis (DM), polymyositis (PM):\n P<\/jats:italic>\n \u00a0<\u00a00.01; immune\u2010mediated necrotizing myopathy (IMNM):\n P<\/jats:italic>\n \u00a0<\u00a00.0001] and adenosine deaminase (ADA) expression (DM:\n P<\/jats:italic>\n \u00a0<\u00a00.001; PM, IMNM:\n P<\/jats:italic>\n \u00a0<\u00a00.0001) in the skeletal muscles, and serum ADA levels [56.7 (95% CI: 53.7, 58.7) vs. 198.8 (95% CI: 186.2, 237.3) ng\/\u03bcL,\n P<\/jats:italic>\n \u00a0<\u00a00.0001]. Intervention with a CD73 inhibitor exacerbated (\n P<\/jats:italic>\n \u00a0=\u00a00.0461), whereas adenosine receptor agonists (A1:\n P<\/jats:italic>\n \u00a0=\u00a00.0009; A2B:\n P<\/jats:italic>\n \u00a0<\u00a00.0001; A3:\n P<\/jats:italic>\n \u00a0=\u00a00.0001) and the HIF\u20101\u03b1 inhibitor (\n P<\/jats:italic>\n \u00a0=\u00a00.0044) alleviated skeletal muscle injury in EAM mice. Elevated expression of programmed cell death protein\u20101 (PD1:\n P<\/jats:italic>\n \u00a0=\u00a00.0023) and T\u2010cell immunoglobulin and mucin\u2010domain containing\u20103 (TIM3:\n P<\/jats:italic>\n \u00a0<\u00a00.0001) in skeletal muscles of patients with IIM were correlated with creatine kinase levels (PD1,\n r<\/jats:italic>\n \u00a0=\u00a00.7072,\n P<\/jats:italic>\n \u00a0<\u00a00.0001; TIM3,\n r<\/jats:italic>\n \u00a0=\u00a00.4808,\n P<\/jats:italic>\n \u00a0=\u00a00.0046). PD1\n +<\/jats:sup>\n CD4\n +<\/jats:sup>\n (\n r<\/jats:italic>\n \u00a0=\u00a00.3243,\n P<\/jats:italic>\n \u00a0=\u00a00.0115) and PD1\n +<\/jats:sup>\n CD8\n +<\/jats:sup>\n (\n r<\/jats:italic>\n \u00a0=\u00a00.3959,\n P<\/jats:italic>\n \u00a0=\u00a00.0017) T cells were correlated with Myositis Disease Activity Assessment Visual Analogue Scale scores (muscle) in IIM. The exhausted Tregs were identified in the skeletal muscles of patients with IIM. Activation of the A2B adenosine receptor downregulated HIF\u20101\u03b1 (protein or mRNA level,\n P<\/jats:italic>\n \u00a0<\u00a00.01), resulting in decreased T helper cell 17 (Th17) (13.58% vs. 5.43%,\n P<\/jats:italic>\n \u00a0=\u00a00.0201) and phosphorylated\u2010signal transducer and activator of transcription 3 (p\u2010STAT3)\n +<\/jats:sup>\n Th17 (16.32% vs. 6.73%,\n P<\/jats:italic>\n \u00a0=\u00a00.0029), decreased exhausted Tregs (PD1\n +<\/jats:sup>\n Tregs: 53.55% vs. 40.28%,\n P<\/jats:italic>\n \u00a0=\u00a00.0005; TIM3\n +<\/jats:sup>\n Tregs: 3.93% vs. 3.11%,\n P<\/jats:italic>\n \u00a0=\u00a00.0029), and increased Tregs (0.45% vs. 2.89%,\n P<\/jats:italic>\n \u00a0=\u00a00.0006) in EAM mice.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The exhausted T cells may be pathogenic in IIM,\u00a0and\u00a0the activation of adenosine A2B receptor signalling pathway can regulate Th17\/Treg balance and inhibit Tregs\u00a0exhaustion, thereby slowing EAM disease progression.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.13581","type":"journal-article","created":{"date-parts":[[2024,9,17]],"date-time":"2024-09-17T14:32:12Z","timestamp":1726583532000},"page":"2460-2475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Adenosine A2B receptor activation regulates the balance between T helper 17 cells and regulatory T cells, and inhibits regulatory T cells exhaustion in experimental autoimmune myositis"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3765-2585","authenticated-orcid":false,"given":"Yueyuan","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Limei","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geng","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of General Practice, General Practice Medical Center West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leiyi","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binhan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7998-6444","authenticated-orcid":false,"given":"Xiaoyan","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology Naval Medical University Shanghai Yangpu District China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6727-1839","authenticated-orcid":false,"given":"Qibing","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology West China Hospital, Sichuan University Chengdu Wuhou District China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,9,16]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"695","article-title":"Epidemiology of the idiopathic inflammatory myopathies, nature reviews","volume":"19","author":"Khoo 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