High-resolution analysis of T cell subsets, clonality, and trajectories in psoriasis

Lesions in psoriasis are enriched for IL-17-associated CD4+ and CD8+ T-cell states with prominent CD8+ Tc17 clonal expansion, and expanded clonotypes contribute more to skin than blood.

• Why it matters: Psoriasis is sustained by type 17 immunity, but transcriptionally defined T-cell states and their clonal organization across lesions, uninvolved skin, and circulation remain unclear.
• What they did: Paired single-cell RNA and TCR sequencing of T cells from two spatially separated lesions, non-lesional skin, and peripheral blood in 23 participants, plus healthy skin and blood comparators, resolved 19 cutaneous T-cell populations.
• The result: T-cell composition separated 57 lesional samples into two recurrent compositional states concordant across paired body sites; HLA-C*06:02 associated with pretreatment CD8+ composition, clonotype overlap, and clonal-size distributions, and therapy showed heterogeneous remodeling in eight treated participants.