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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2025
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| _version_ | 1852014057250357248 |
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| 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 | |
| repository_id_str | |
| 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 |