Single-cell profiling reveals CCL5Hi GZMAHi effector memory CD8 T cell association to oligoarticular JIA

Area of Science:

• Immunology
• Rheumatology
• Genomics

Background:

• Oligoarticular juvenile idiopathic arthritis (oligo JIA) is the most common subtype of JIA.
• Uveitis is a frequent and sight-threatening comorbidity of oligo JIA.
• The precise immunopathogenic mechanisms driving oligo JIA and its extra-articular manifestations are not fully understood.

Purpose of the Study:

• To comprehensively characterize the immune landscape in oligo JIA.
• To identify specific pathogenic immune cell populations involved in oligo JIA.
• To uncover regulatory mechanisms contributing to oligo JIA and associated uveitis.

Main Methods:

• Single-cell RNA and T cell receptor sequencing (scRNA/TCR-Seq) on peripheral blood mononuclear cells (PBMC) and synovial fluid (SF).
• Analysis of cellular composition, gene expression, and T cell clonality in treatment-naïve oligo JIA patients and healthy controls.
• Validation of key findings using mass cytometry (CyTOF) in an independent patient cohort.

Main Results:

• Enrichment of activated CD8+ effector memory T cells (CD8+TEM), intermediate monocytes, and regulatory T cells was observed in SF.
• CD8+TEM cells showed increased expression of CCL5, GZMA, and GNLY, with significant clonal expansion, and were depleted in blood.
• In oligo JIA patients with uveitis, mucosal-associated invariant T (MAIT) cells exhibited clonal expansion and cytotoxic signatures.

Conclusions:

• Clonally expanded, cytotoxic CD8+ TEM cells are key drivers of joint inflammation in oligo JIA.
• Activated MAIT and NK cells in patients with uveitis indicate broader systemic immune activation.
• These identified cell populations represent potential therapeutic targets for oligo JIA and its ocular complications.