Single-cell analysis reveals CXCL16⁺ dendritic cells and clonally expanded GZMK⁺ CD4 T cells driving joint inflammation in psoriatic arthritis.

Authors

Briana J Mullins, Jasmine Shwetar, Alberto Herrera, Anthony Youzhi Cheng, Katharine Lu Yang, Anthony Jiménez Hernández, Katie Tumang, Eleni P Mimitou, Ali Sahimi, Luz Alvarado, Rhina Medina, Rebecca H Haberman, Parvathy V Girija, Thomas Boehringer, Ellie Ivanova, Timothy C Borbet, Stephanie Eichman, Ian Cunningham, Kirsty Hillier, Sofia Bajwa, Celiane Cardoso Carvalho, Susan R Schwab, Mukundan G Attur, Kelly Ruggles, José U Scher, Sergei B Koralov

Published in

Arthritis & rheumatology (Hoboken, N.J.). Oct 20, 2026. Epub Oct 20, 2026.

Abstract

Psoriatic arthritis (PsA) is a chronic immune-mediated arthritis affecting approximately 30% of individuals with psoriasis. The mechanisms driving PsA joint inflammation remain incompletely defined.
To address this gap, we performed multimodal single-cell sequencing of immune cells from matched peripheral blood and synovial fluid (SF) from 6 PsA patients, with comparisons to a rheumatoid arthritis (RA) patient and 6 healthy controls (HC).
SF CD4 and CD8 T cells displayed elevated expression of TOX, PDCD1, CTLA4, GZMK, CXCR3, and CXCR6, reflecting a tissue-specific activation state. CD4 T cell sub-clustering revealed clonally expanded populations enriched for GZMK and cytotoxic gene programs, suggesting antigen-driven activation. In contrast, CD8 T cell clonality showed a significant correlation with GZMK expression, however GZMK⁺ CD8 T cells in the joint exhibited a transcriptional signature consistent with functional exhaustion. Concurrently, SF was enriched for CD141⁺, CD1c⁺, CCR7⁺, and SIGLEC6⁺ dendritic cells (DCs), characterized by increased CXCL16 expression and antigen presentation pathways. Flow cytometry and ELISA in an additional 25 PsA patients and 16 HCs confirmed protein-level enrichment of key chemokines and GZMK⁺ T cells. Cell-cell communication analysis highlighted CXCR6-CXCL16 and CXCR3-CXCL10 chemokine axes as mediators of immune cell recruitment and retention, while in vitro assays showed enhanced migration of PsA SF T cells toward a CXCL16 gradient relative to paired blood.
Together, these findings suggest that clonally expanded GZMK⁺ CD4 T cells in PsA are cytotoxic and antigen-responsive, contributing to joint inflammation following recruitment by CXCL16-producing dendritic cells.

PMID:
42901778
Bibliographic data and abstract were imported from PubMed on 21 Oct 2026.

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