ArticleArthritis and rheumatism2013
Death receptor 5-targeted depletion of interleukin-23-producing macrophages, Th17, and Th1/17 associated with defective tyrosine phosphatase in mice and patients with rheumatoid arthritis.
Article in Arthritis and rheumatism, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- GTS-21 modulates rheumatoid arthritis Th17 and Th2 lymphocyte subset differentiation through the ɑ7nAch receptor.Clinical rheumatology · 2025Article
- TRAIL promotes the polarization of human macrophages toward a proinflammatory M1 phenotype and is associated with increased survival in cancer patients with high tumor macrophage content.Frontiers in immunology · 2023Article
- sDR5-Fc inhibits macrophage M1 polarization by blocking the glycolysis.Journal of geriatric cardiology : JGC · 2021Article
- Modulation of TCR Signaling by Tyrosine Phosphatases: From Autoimmunity to Immunotherapy.Frontiers in cell and developmental biology · 2020Review
- Review
- CysLT1 receptor antagonist alleviates pathogenesis of collagen-induced arthritis mouse model.Oncotarget · 2017Article
- Review
- Semaphorin 7A as a potential immune regulator and promising therapeutic target in rheumatoid arthritis.Arthritis research & therapy · 2017Article
- Protein tyrosine phosphatase SHP-1: resurgence as new drug target for human autoimmune disorders.Immunologic research · 2016Review
- Anti-DR5 mAb inhibits proliferation of human fibroblast-like synovial cells and reduces their cytokine secretion in vitro.OncoTargets and therapy · 2015Article
- Inhibition of fucosylation reshapes inflammatory macrophages and suppresses type II collagen-induced arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2014Article
- The Dynamic Duo-Inflammatory M1 macrophages and Th17 cells in Rheumatic Diseases.Journal of orthopedics & rheumatology · 2013Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveBidirectional interactions between granulocyte-macrophage colony-stimulating factor-positive (GM-CSF+) T cells and interferon regulatory factor 5-positive (IRF-5+) macrophages play a major role in autoimmunity. In the absence of SH2 domain-containing phosphatase 1 (SHP-1), GM-CSF-stimulated cells are resistant to death receptor (DR)-mediated apoptosis. The objective of this study was to determine whether TRA-8, an anti-DR5 agonistic antibody, can eliminate inflammatory macrophages and CD4 T cells in the SHP-1-deficient condition.
methodsUbiquitous Cre (Ubc.Cre) human/mouse-chimeric DR5-transgenic mice were crossed with viable SHP-1-defective motheaten (mev/mev) mice. TRA-8 was administered weekly for up to 4 weeks. The clinical scores, histopathologic severity, and macrophage and CD4 T cell phenotypes were evaluated. The role of TRA-8 in depleting inflammatory macrophages and CD4 T cells was also evaluated, using synovial fluid obtained from patients with rheumatoid arthritis (RA).
resultsThe levels of inflammatory macrophages (interleukin-23-positive [IL-23+] IRF-5+) and CD4 T cells (IL-17+ GM-CSF+) were elevated in mev/mev mice. In DR5-transgenic mev/mev mice, DR5 expression was up-regulated in these 2 cell populations. TRA-8 treatment depleted these cell populations and resulted in a significant reduction in inflammation and in the titers of autoantibodies. In synovial cells from patients with RA, the expression of IRF5 and DR5 was negatively correlated with the expression of PTPN6. TRA-8, but not TRAIL, suppressed RA inflammatory macrophages and Th17 cells under conditions in which the expression of SHP-1 is low.
conclusionIn contrast to TRAIL, which lacks the capability to counteract the survival signal in the absence of SHP-1, TRA-8 eliminated both IRF-5+ IL-23+ M1 macrophages and pathogenic GM-CSF+ IL-17+ CD4 T cells in a SHP-1-independent manner. The results of the current study suggest that TRA-8 can deplete inflammatory cell populations that result from a hyperactive GM-CSF/IRF-5 axis.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.