IL-7-glucose-Aiolos axis orchestrates pathogenic CD8⁺ T cell function in spondyloarthritis

Area of Science:

• Immunology
• Metabolic pathways
• Inflammatory diseases

Background:

• CD8+ T cells are key in immunity but also implicated in inflammatory conditions like spondyloarthritis.
• Understanding the molecular basis of human CD8+ T cell effector function is crucial.

Purpose of the Study:

• To identify and characterize a distinct subset of human CD8+ T cells involved in inflammatory processes.
• To elucidate the role of metabolic state and transcriptional regulation in CD8+ T cell effector function.

Main Methods:

• Flow cytometry to identify CD8+ T cell subsets based on CXCR3, IL-7R, GLUT1, and Aiolos expression.
• Analysis of IL-7-JAK-STAT signaling and its impact on GLUT1 and Aiolos.
• Assessment of CD8+ T cells in patients with spondyloarthritis, rheumatoid arthritis, and healthy controls.
• Evaluation of JAK inhibitor therapy effects on CD8+ T cell phenotype and clinical outcomes.

Main Results:

• A metabolically active CD8+ T cell subset (CXCR3+, IL-7R+, GLUT1+, Aioloslow) was identified.
• IL-7 signaling promotes GLUT1 expression and glucose uptake while reducing Aiolos.
• This Aioloslow subset is enriched in inflamed joints of spondyloarthritis patients and correlates with disease activity.
• JAK inhibitor therapy decreased GLUT1, increased Aiolos, reduced cytokine production, and improved clinical symptoms.

Conclusions:

• Cytokine signaling, metabolic status, and gene transcription are interconnected in human CD8+ T cells.
• Aiolos acts as a regulatory point integrating these signals, influencing effector function in inflammatory diseases.
• Targeting this CD8+ T cell subset and its metabolic activity offers a potential therapeutic strategy for spondyloarthritis.