Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx

Introduction<p>Dysregulated T cell homeostasis leading to enhanced immune responses is a critical pathogenic mechanism in rheumatoid arthritis (RA). Programmed cell death protein 1 (PD-1) is a crucial immune checkpoint that modulates T cell activity. Soluble PD-1 (sPD-1) may contribute to the...

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Main Author: Chao Yang (174810) (author)
Other Authors: Miao Ma (8351802) (author), Kangjie Yu (8620416) (author), Yi Wang (32470) (author), Yuting Zhang (337082) (author), Yan Shen (12156) (author), Jun Wang (5906) (author), Xiaoke Wang (548086) (author), Lulu Luo (11884589) (author), Ya Zhao (807581) (author)
Published: 2025
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_version_ 1852014057250357248
author Chao Yang (174810)
author2 Miao Ma (8351802)
Kangjie Yu (8620416)
Yi Wang (32470)
Yuting Zhang (337082)
Yan Shen (12156)
Jun Wang (5906)
Xiaoke Wang (548086)
Lulu Luo (11884589)
Ya Zhao (807581)
author2_role author
author
author
author
author
author
author
author
author
author_facet Chao Yang (174810)
Miao Ma (8351802)
Kangjie Yu (8620416)
Yi Wang (32470)
Yuting Zhang (337082)
Yan Shen (12156)
Jun Wang (5906)
Xiaoke Wang (548086)
Lulu Luo (11884589)
Ya Zhao (807581)
author_role author
dc.creator.none.fl_str_mv Chao Yang (174810)
Miao Ma (8351802)
Kangjie Yu (8620416)
Yi Wang (32470)
Yuting Zhang (337082)
Yan Shen (12156)
Jun Wang (5906)
Xiaoke Wang (548086)
Lulu Luo (11884589)
Ya Zhao (807581)
dc.date.none.fl_str_mv 2025-12-10T06:31:47Z
dc.identifier.none.fl_str_mv 10.3389/fimmu.2025.1665078.s001
dc.relation.none.fl_str_mv https://figshare.com/articles/dataset/Table_1_Fibroblast-like_synoviocytes_mediate_the_generation_of_soluble_PD-1_in_an_MMP-9-dependent_manner_a_novel_target_therapy_for_rheumatoid_arthritis_docx/30845966
dc.rights.none.fl_str_mv CC BY 4.0
info:eu-repo/semantics/openAccess
dc.subject.none.fl_str_mv Genetic Immunology
rheumatoid arthritis (RA)
fibroblast-like synoviocytes (FLS)
soluble PD-1
MMP-9
PD-L1-MSA
dc.title.none.fl_str_mv Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
dc.type.none.fl_str_mv Dataset
info:eu-repo/semantics/publishedVersion
dataset
description Introduction<p>Dysregulated T cell homeostasis leading to enhanced immune responses is a critical pathogenic mechanism in rheumatoid arthritis (RA). Programmed cell death protein 1 (PD-1) is a crucial immune checkpoint that modulates T cell activity. Soluble PD-1 (sPD-1) may contribute to the sustained activation of T cells. Investigating the mechanisms of sPD-1 production and its role in RA pathogenesis is essential for the development of alternative treatment strategies.</p>Methods<p>A total of 122 patients with RA and 68 Health controls were enrolled in this study. We assessed PD-1 expression in T cells from patients with RA and measured sPD-1 levels in plasma, revealing a correlation between sPD-1 and disease activity progression in patients with RA. Furthermore, we examined the potential mechanisms underlying sPD-1 production in RA patients. Additionally, we evaluated the therapeutic effects of PD-L1-MSA, a fusion protein containing C-terminal PD-L1 and full-length MSA, in collagen-induced arthritis (CIA) mice.</p>Results<p>Clinical analyses indicated that plasma sPD-1 levels positively correlated with indicators of disease activity. The generation of sPD-1 primarily resulted from matrix metalloproteinase-9 (MMP-9)-mediated shedding of surface PD-1 from activated T cells, with MMP-9 being derived from fibroblast-like synoviocytes (FLS). Additionally, therapeutic evaluation in collagen-induced arthritis (CIA) mice demonstrated that PD-L1-MSA, a fusion protein containing C-terminal PD-L1 and full-length mouse serum albumin (MSA), significantly mitigated pathological changes.</p>Discussion<p>These results indicate that plasma sPD-1 levels are positively associated with RA disease activity, supporting its potential as a complementary biomarker for monitoring disease activity (especially in combination with traditional indicators like CRP/ESR), though its standalone diagnostic value requires further validation. Furthermore, targeting sPD-1, such as with PD-L1-MSA, represents a promising complementary therapeutic candidate for alleviating RA pathology.</p>
eu_rights_str_mv openAccess
id Manara_693cde89dbcaf89d342bf1dfe0ea7604
identifier_str_mv 10.3389/fimmu.2025.1665078.s001
network_acronym_str Manara
network_name_str ManaraRepo
oai_identifier_str oai:figshare.com:article/30845966
publishDate 2025
repository.mail.fl_str_mv
repository.name.fl_str_mv
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rights_invalid_str_mv CC BY 4.0
spelling Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docxChao Yang (174810)Miao Ma (8351802)Kangjie Yu (8620416)Yi Wang (32470)Yuting Zhang (337082)Yan Shen (12156)Jun Wang (5906)Xiaoke Wang (548086)Lulu Luo (11884589)Ya Zhao (807581)Genetic Immunologyrheumatoid arthritis (RA)fibroblast-like synoviocytes (FLS)soluble PD-1MMP-9PD-L1-MSAIntroduction<p>Dysregulated T cell homeostasis leading to enhanced immune responses is a critical pathogenic mechanism in rheumatoid arthritis (RA). Programmed cell death protein 1 (PD-1) is a crucial immune checkpoint that modulates T cell activity. Soluble PD-1 (sPD-1) may contribute to the sustained activation of T cells. Investigating the mechanisms of sPD-1 production and its role in RA pathogenesis is essential for the development of alternative treatment strategies.</p>Methods<p>A total of 122 patients with RA and 68 Health controls were enrolled in this study. We assessed PD-1 expression in T cells from patients with RA and measured sPD-1 levels in plasma, revealing a correlation between sPD-1 and disease activity progression in patients with RA. Furthermore, we examined the potential mechanisms underlying sPD-1 production in RA patients. Additionally, we evaluated the therapeutic effects of PD-L1-MSA, a fusion protein containing C-terminal PD-L1 and full-length MSA, in collagen-induced arthritis (CIA) mice.</p>Results<p>Clinical analyses indicated that plasma sPD-1 levels positively correlated with indicators of disease activity. The generation of sPD-1 primarily resulted from matrix metalloproteinase-9 (MMP-9)-mediated shedding of surface PD-1 from activated T cells, with MMP-9 being derived from fibroblast-like synoviocytes (FLS). Additionally, therapeutic evaluation in collagen-induced arthritis (CIA) mice demonstrated that PD-L1-MSA, a fusion protein containing C-terminal PD-L1 and full-length mouse serum albumin (MSA), significantly mitigated pathological changes.</p>Discussion<p>These results indicate that plasma sPD-1 levels are positively associated with RA disease activity, supporting its potential as a complementary biomarker for monitoring disease activity (especially in combination with traditional indicators like CRP/ESR), though its standalone diagnostic value requires further validation. Furthermore, targeting sPD-1, such as with PD-L1-MSA, represents a promising complementary therapeutic candidate for alleviating RA pathology.</p>2025-12-10T06:31:47ZDatasetinfo:eu-repo/semantics/publishedVersiondataset10.3389/fimmu.2025.1665078.s001https://figshare.com/articles/dataset/Table_1_Fibroblast-like_synoviocytes_mediate_the_generation_of_soluble_PD-1_in_an_MMP-9-dependent_manner_a_novel_target_therapy_for_rheumatoid_arthritis_docx/30845966CC BY 4.0info:eu-repo/semantics/openAccessoai:figshare.com:article/308459662025-12-10T06:31:47Z
spellingShingle Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
Chao Yang (174810)
Genetic Immunology
rheumatoid arthritis (RA)
fibroblast-like synoviocytes (FLS)
soluble PD-1
MMP-9
PD-L1-MSA
status_str publishedVersion
title Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
title_full Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
title_fullStr Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
title_full_unstemmed Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
title_short Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
title_sort Table 1_Fibroblast-like synoviocytes mediate the generation of soluble PD-1 in an MMP-9-dependent manner: a novel target therapy for rheumatoid arthritis.docx
topic Genetic Immunology
rheumatoid arthritis (RA)
fibroblast-like synoviocytes (FLS)
soluble PD-1
MMP-9
PD-L1-MSA