Synovial fibroblasts in juvenile idiopathic arthritis: A scoping review

Lomholt, Søren; Pedersen, Malthe Jessen; Glerup, Mia; Kragstrup, Tue Wenzel

doi:10.1016/j.semarthrit.2022.152159

Cited by 3 publications

(3 citation statements)

References 45 publications

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“…Here, we instead investigated the contribution of S-Fib in driving neutrophil activation. Data on S-Fib from arthritis patients show that they are heterogenous and potent cytokine producers with altered surface marker expression and may thus influence neutrophil function in several ways ( 8 , 20 ). Indeed, studies in RA show a clear interaction between S-Fib and neutrophils.…”

Section: Discussionmentioning

confidence: 99%

“…Synovial fibroblasts (S-Fib) are gaining increasing attention as drivers of inflammation in arthritic diseases [such as rheumatoid arthritis (RA)], e.g., as activators of immune cells ( 8 ). For example, S-Fib drive metabolic alterations in macrophages, resulting in increased viability, whilst macrophages promote fibroblast invasiveness ( 9 , 10 ).…”

Section: Introductionmentioning

confidence: 99%

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Synovial fibroblasts from children with oligoarticular juvenile idiopathic arthritis induce migration and prolong viability of neutrophils

Schmidt,

Mossberg,

Berthold

et al. 2024

Front. Pediatr.

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IntroductionLittle is known of the processes that trigger neutrophil activation in the joint of patients with oligoarticular juvenile idiopathic arthritis (oJIA), and if synovial fibroblasts (S-Fib) play an important role in the activation. Therefore, we aimed to investigate whether S-Fib derived from oJIA patients drive neutrophil activation.MethodsSynovial fluid (SF) was collected from patients with oJIA. S-Fib were isolated from the SF of n = 7 patients through passaging. Subsequently, the S-Fib were primed or not with 20% of pooled SF. Supernatants were used to study migration of neutrophils in a transwell system. Additionally, the influence of S-Fib on neutrophils were studied in co-cultures. Phenotype and viability were assessed by flow cytometry. Neutrophil function was tested through the production of reactive oxygen species (ROS), and supernatants were tested for myeloperoxidase (MPO) release and elastase activity.ResultsSupernatants of S-Fib induced neutrophil migration (n = 5, p = 0.0491), which was further pronounced using supernatants from SF-primed S-Fib (p = 0.0063). Additionally, co-culture between SF-primed S-Fib and neutrophils resulted in prolonged viability (n = 5, p = 0.0094), with little effect on activation markers, e.g., CD11b. Conversely, co-culture did not induce functional alterations (n = 4), such as production of ROS (p > 0.1570), release of MPO (p > 0.4934) or elastase activity (p > 0.0904). Finally, supernatant stimulation did not replicate the results of prolonged viability (p = 0.9102), suggesting a role of cell-contact.ConclusionS-Fib from patients with oJIA induce migration of neutrophils via soluble mediators and, in addition, S-Fib prolong neutrophil viability in a cell-contact dependent manner. These mechanisms could be important for accumulation of neutrophils during arthritis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synovial fibroblasts from children with oligoarticular juvenile idiopathic arthritis induce migration and prolong viability of neutrophils

Schmidt,

Mossberg,

Berthold

et al. 2024

Front. Pediatr.

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“…In addition to their ability to destroy joint tissue directly, synovial fibroblasts can also act as APCs and eventually stimulate pathogenic T lymphocytes [ 56 ]. It has been shown that SF can activate MHCII-restricted T cell hybridomas specific for arthritogenic peptides [ 57 ].…”

Section: Introductionmentioning

confidence: 99%

NIH/3T3 Fibroblasts Selectively Activate T Cells Specific for Posttranslationally Modified Collagen Type II

Dzhambazov

Batsalova

Mehlen³

et al. 2023

IJMS

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It has been shown that synovial fibroblasts (SF) play a key role in the initiation of inflammation and joint destruction, leading to arthritis progression. Fibroblasts may express major histocompatibility complex class II region (MHCII) molecules, and thus, they could be able to process and present antigens to immunocompetent cells. Here we examine whether different types of fibroblasts (synovial, dermal, and thymic murine fibroblasts, destructive LS48 fibroblasts, and noninvasive NIH/3T3 fibroblasts) may be involved in the initiation of rheumatoid arthritis (RA) pathogenesis and can process and present type II collagen (COL2)—an autoantigen associated with RA. Using a panel of MHCII/Aq-restricted T-cell hybridoma lines that specifically recognize an immunodominant COL2 epitope (COL2259–273), we found that NIH/3T3 fibroblasts activate several T-cell clones that recognize the posttranslationally glycosylated or hydroxylated COL2259–273 epitope. The HCQ.3 hybridoma, which is specific for the glycosylated immunodominant COL2 epitope 259–273 (Gal264), showed the strongest response. Interestingly, NIH/3T3 cells, but not destructive LS48 fibroblasts, synovial, dermal, or thymic fibroblasts, were able to stimulate the HCQ.3 hybridoma and other COL2-specific T-cell hybridomas. Our experiments revealed that NIH/3T3 fibroblasts are able to activate COL2-specific T-cell hybridomas even in the absence of COL2 or a posttranslationally modified COL2 peptide. The mechanism of this unusual activation is contact-dependent and involves the T-cell receptor (TCR) complex.

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