Linking Skin and Joint Inflammation in Psoriatic Arthritis through Shared CD8⁺ T Cell Clones

Area of Science:

• Immunology
• Dermatology
• Rheumatology

Background:

• Psoriatic arthritis (PsA) affects up to 30% of psoriasis patients.
• PsA is an inflammatory arthritis associated with HLA class I.
• The link between skin and joint inflammation in PsA is not fully understood.

Purpose of the Study:

• To test the hypothesis that skin and joint inflammation in PsA are linked.
• To investigate the role of CD8+ T-cell phenotype and clonality in PsA.
• To compare T-cell characteristics between skin and synovial compartments in PsA.

Main Methods:

• Single-cell RNA sequencing (scRNAseq) of skin, synovial tissue, and synovial fluid from PsA patients.
• Spatial transcriptomics of paired and unpaired skin and synovial biopsies.
• Comparison of transcriptional signatures, T-cell receptor (TCR) repertoires, and cell neighborhoods.

Main Results:

• Enrichment of type-17 CD8+ tissue-resident memory (T_RM) T-cells in both skin and joints.
• CD8+ T_RM cells exhibit distinct neighborhoods but are adjacent to antigen-presenting cells.
• 155 CD8+ T-cell clones were shared between skin and joint, with similar cytotoxic, tissue-resident phenotypes.

Conclusions:

• Skin and joint inflammation in PsA are linked via CD8+ T-cell clonality.
• Specific CD8+ T-cells migrate between skin and joint compartments.
• This migration propagates inflammation in PsA.