Juvenile idiopathic arthritis:lymphocyte activation gene-3 is a central immune receptor in children with oligoarticular subtypes
| Autor: | Stinne Ravn Greisen, Seza Ozen, Cæcilie Skejø, E. Sag, Maithri Prasad Aspari, Egemen Turhan, Selcan Demir, Morten Aagaard Nielsen, Malene Hvid, Bent Deleuran, Yelda Bilginer |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
business.industry
T cell Arthritis medicine.disease Pathogenesis 03 medical and health sciences 0302 clinical medicine medicine.anatomical_structure 030225 pediatrics Pediatrics Perinatology and Child Health Immunology medicine Synovial fluid Cytotoxic T cell Cytokine secretion Oligoarticular Juvenile Idiopathic Arthritis business 030217 neurology & neurosurgery Ex vivo |
| Zdroj: | Sag, E, Demir, S, Aspari, M, Nielsen, M A, Skejø, C, Hvid, M, Turhan, E, Bilginer, Y, Greisen, S, Ozen, S & Deleuran, B 2021, ' Juvenile idiopathic arthritis : lymphocyte activation gene-3 is a central immune receptor in children with oligoarticular subtypes ', Pediatric Research, vol. 90, no. 4, pp. 744-751 . https://doi.org/10.1038/s41390-021-01588-2 |
| DOI: | 10.1038/s41390-021-01588-2 |
| Popis: | Background: We investigated the role of inhibitory receptors (IRs) and especially lymphocyte activation gene-3 (LAG-3) in the pathogenesis of oligoarticular juvenile idiopathic arthritis (o-JIA). Methods: Paired samples of synovial fluid (SF) and plasma and peripheral blood (PBMCs) and synovial fluid mononuclear cells (SFMCs) were collected from o-JIA patients along with their clinical data (n = 24). Plasma from healthy controls (n = 14) and paired SF and plasma samples from five non-arthritic juvenile orthopedic patients (n = 5) served as controls. Spontaneously differentiated fibroblast-like synoviocytes (FLSs) from SFMCs were co-cultured with autologous PBMCs/SFMCs and used as ex vivo disease model. Soluble levels and cellular expressions of IRs together with their functional properties in the ex vivo model were analyzed. Results: In patients with o-JIA, soluble levels of LAG-3 and expression of LAG-3 and T cell immunoglobulin mucin03 (TIM-3) on CD3+CD4+CD45RO+ T cells were increased, especially in SF. Major histocompatibility complex (MHC) class II expression was induced on FLSs when these were co-cultured with autologous PBMCs/SFMCs, together with an increased monocyte chemoattractant protein-1 (MCP-1) production. In PBMC and FLS + PBMC co-cultures, neutralizing antibodies to IRs were added. Only anti-LAG-3 antibodies significantly increased MCP-1 secretion. The addition of agonistic LAG-3 antibody resulted in decreased effector cytokine secretion. Conclusions: This is the first report comparing the effects of different IRs in o-JIA and suggests that LAG-3 might contribute to the pathogenesis of this disease. Impact: This is the first study addressing the role of different co-IRs in o-JIA.We showed that LAG-3 and TIM-3 seem more important in juvenile arthritis in contrast to adult rheumatoid arthritis, where cytotoxic T-lymphocyte-associated antigen-4 and programmed cell death-1 were reported to be more important.We designed an ex vivo disease model for o-JIA, examined the effects of co-IRs in this model, and demonstrated that they might contribute to the pathogenesis of the disease.LAG-3 might play a role in o-JIA pathogenesis and might be a potential therapeutic option for o-JIA patients. |
| Databáze: | OpenAIRE |
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