مورد إلكتروني
Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis
| العنوان: | Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis |
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| المصدر: | Pedersen , J M , Hansen , A S , Skejø , C , Juul-Madsen , K , Junker , P , Hørslev-Petersen , K , Hetland , M L , Stengaard-Pedersen , K , Østergaard , M , Møller , B K , Dreyer , L , Hauge , E M , Hvid , M , Greisen , S & Deleuran , B 2023 , ' Lymphocyte activation gene 3 is increased and affects cytokine production in rheumatoid arthritis ' , Arthritis Research and Therapy , vol. 25 , no. 1 , 97 . |
| بيانات النشر: | 2023 |
| تفاصيل مُضافة: | Pedersen, Janni Maria Hansen, Aida Solhøj Skejø, Cæcilie Juul-Madsen, Kristian Junker, Peter Hørslev-Petersen, Kim Hetland, Merete Lund Stengaard-Pedersen, Kristian Østergaard, Mikkel Møller, Bjarne Kuno Dreyer, Lene Hauge, Ellen Margrethe Hvid, Malene Greisen, Stinne Deleuran, Bent |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | Background: Lymphocyte activation gene-3 (LAG-3) inhibits T cell activation and interferes with the immune response by binding to MHC-II. As antigen presentation is central in rheumatoid arthritis (RA) pathogenesis, we studied aspects of LAG-3 as a serological marker and mediator in the pathogenesis of RA. Since Galectin-3 (Gal-3) is described as an additional binding partner for LAG-3, we also aimed to study the functional importance of this interaction. Methods: Plasma levels of soluble (s) LAG-3 were measured in early RA patients (eRA, n = 99) at baseline and after 12 months on a treat-to-target protocol, in self-reportedly healthy controls (HC, n = 32), and in paired plasma and synovial fluid (SF) from chronic RA patients (cRA, n = 38). Peripheral blood mononuclear cells (PBMCs) and synovial fluid mononuclear cells (SFMCs) were examined for LAG-3 expression by flow cytometry. The binding and functional outcomes of LAG-3 and Gal-3 interaction were assessed with surface plasmon resonance (SPR) and in cell cultures using rh-LAG3, an antagonistic LAG-3 antibody and a Gal-3 inhibitor. Results: Baseline sLAG-3 in the plasma was increased in eRA compared to HC and remained significantly elevated throughout 12 months of treatment. A high level of sLAG-3 at baseline was associated with the presence of IgM-RF and anti-CCP as well as radiographic progression. In cRA, sLAG-3 was significantly increased in SF compared with plasma, and LAG-3 was primarily expressed by activated T cells in SFMCs compared to PBMCs. Adding recombinant human LAG-3 to RA cell cultures resulted in decreased cytokine secretion, whereas blocking LAG-3 with an antagonistic antibody resulted in increased cytokine secretion. By SPR, we found a dose-dependent binding between LAG-3 and Gal-3. However, inhibiting Gal-3 in cultures did not further change cytokine production. Conclusions: sLAG-3 in the plasma and synovial fluid is increased in both early and chronic RA patients, particularly in the inflam |
| مصطلحات الفهرس: | Co-inhibitory receptors, Galectin-3, Inflammation, LAG-3, Rheumatoid arthritis, article |
| URL: | |
| الإتاحة: | Open access content. Open access content info:eu-repo/semantics/openAccess |
| ملاحظة: | application/pdf English |
| أرقام أخرى: | DAV oai:pure.atira.dk:publications/02afac4b-0732-44cd-a1a9-44d823e51fcb 1414369131 |
| المصدر المساهم: | UNIV OF COPENHAGEN From OAIster®, provided by the OCLC Cooperative. |
| رقم الانضمام: | edsoai.on1414369131 |
| قاعدة البيانات: | OAIster |
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