Immune Checkpoint Therapy in Juvenile Idiopathic Arthritis (JIA)

Creative Biolabs offers comprehensive and integrated immune checkpoint services, providing theoretical support for immune checkpoint therapy in juvenile idiopathic arthritis (JIA) to our esteemed clients worldwide.

T-cell Immunity and JIA

JIA, the most prevalent chronic rheumatic disease in childhood, is driven by T cell-mediated tissue inflammation. Consequently, intervention strategies targeting T-cell immune checkpoints have emerged as significant potential interventions for JIA. T-cell involvement in JIA pathogenesis encompasses:

Th1 cells promote leukocyte accumulation within inflamed joints.
Th17 cells induce cartilage degradation through stimulation of synovial fibroblasts.
Th17 cells may transform into Th1 cells during chronic inflammatory processes.

JIA and immune cells. (Bella, et al., 2023) Fig 1. JIA and immune cells.¹

JIA-associated Immune Checkpoint Molecules

Numerous pivotal immune checkpoint molecules have been implicated in JIA pathogenesis, serving as potential therapeutic targets. Notably:

Memory CD4⁺ T cells derived from JIA patient synovial fluid exhibit significantly elevated levels of CTLA-4, PD-1, and TIM-3.
LAG-3 plays an integral role in cytokine production during JIA pathogenesis.
Elevated levels of CD40 in synovial fluid facilitate the onset of joint inflammation.

Strategies for Immune Checkpoint Intervention in JIA

Cutting-edge JIA-focused immune checkpoint intervention strategies, encompassing ligand-Fc fusion proteins, agonistic antibodies, bispecific antibodies, and engineered antibodies, are currently under development. These strategies aim to enhance the pathological progression of autoimmune rheumatic diseases. Some notable strategies include:

Antibodies targeting LAG-3 effectively modulate cytokine production within in vitro co-culture models.
PD-1-targeted interventions directly improve the activity of T-cell populations, independent of cytokine signaling conditions.
CTLA-4-Fc effectively ameliorates symptoms in JIA patients, exhibiting a favorable safety profile.

Research Status

Title: Clonally expanded PD-1-expressing T cells are enriched in synovial fluid of juvenile idiopathic arthritis patients

Research Objective:

To elucidate the roles of immune checkpoints and T lymphocyte activity in the pathogenesis of JIA and chronic inflammation.

Methodology:

The investigation involved transcriptomic analysis via RNA sequencing to assess gene expression changes. Additionally, flow cytometry was utilized to explore protein profiles, enabling the characterization of T-cell characteristics during chronic inflammation in JIA at the single-cell level.

Research Findings:

The study revealed the presence of clonally expanded tissue-resident memory-like cells expressing notably high levels of PD-1. These cells displayed potent pro-inflammatory capabilities and sustained in situ chronic inflammation in JIA pathogenesis. Consequently, targeting PD-1 as a novel therapeutic strategy holds promise for effectively addressing JIA by directly modulating hyperactive T-cell responses, regardless of cytokine secretion considerations.

Fig.2 Increased expression of inhibitory checkpoint molecules by SF-infiltrating CD4⁺ T cells.²

Our Services

At Creative Biolabs, we strive to deliver exceptional service quality and continuous innovation in immune checkpoint research. We offer customized consulting services, leveraging the expertise of our scientists and technical professionals. With state-of-the-art facilities and cutting-edge technology, we deliver precise and reliable experimental services. Whether it is RNA sequencing, protein analysis, or flow cytometry, we ensure high-quality results with strict adherence to standardized protocols and rigorous quality control measures. We invite you to contact us today to collaborate with our team.

References

Bella, Rinaldi, et al. "Genetic Background and Molecular Mechanisms of Juvenile Idiopathic Arthritis." International Journal of Molecular Sciences. 24 (2023): 1846.
Vanni, Mazzoni, et al. "Clonally expanded PD-1-expressing T cells are enriched in synovial fluid of juvenile idiopathic arthritis patients." Immunodeficiencies and autoimmunity. 53 (2022): 162.

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