T cells form distinct spatially restricted immune responses in synovium of patients with psoriasis arthritis and rheumatoid arthritis.

Authors

Nathalie J Behr, Julio Ramírez, Ana B Azuaga, Raquel Celis, Gerd Geisslinger, Frank Behrens, Stefano Alivernini, Juan D Cañete, Klaus Scholich

Published in

Frontiers in immunology. Volume 17. Pages 1946638. Epub Sep 30, 2026.

Abstract

Psoriatic arthritis (PsA) and rheumatoid arthritis (RA) are chronic, inflammatory joint diseases, causing progressive structural damage. Non-immune cells, such as stromal fibroblasts promote inflammation, cartilage degradation and bone resorption in the synovium. Here, we hypothesized that lining fibroblasts have distinct immune cell neighborhoods in PsA and RA.
The spatial distribution of structural and immune cell populations was determined using high-multiplex immunohistochemistry in synovial biopsies from 9 PsA and 6 RA patients without previous methotrexate (MTX) treatment and 11 PsA and 11 RA patients treated with MTX treatment.
Dendritic cells and macrophages exhibited strong patient-specific variability, whereas the numbers and localization of T cell subpopulations displayed patterns specific to the disease and treatment. Quantification of overall cell numbers in the synovium revealed a higher Th1/Th2 ratio in PsA than in RA. MTX-treated PsA, patients showed lower Th1 and higher Th2 numbers, whereas in RA, Th1, Th2 and Th9 numbers were less abundant. Spatial analysis revealed two regions with distinct immune responses around the lining fibroblasts. In PsA, the immediate vicinity of the lining fibroblasts was dominated by Th1/Th17 cells, followed by a region with a predominant Th2/Th9 cell population. In RA, a barrier-focused immune response consisting of Th9, Th17, and Th22 cells was observed near the lining fibroblasts. MTX-treated patients had lower the number of Th cells near the lining fibroblasts in PsA but did not differ in Th subtype patterns. In RA, lower Th numbers were mainly observed in the immediate vicinity of the lining fibroblasts, with distinct alterations in the numbers of Th22 and Th2 cells.
In PsA, the immediate vicinity of lining fibroblasts is dominated by Th1/Th17/DC2 cells. In RA, a Th9/Th17/Th22 barrier-centered immune response was present near the lining; Th1 and Th2 cells were essentially absent. Patients treated with MTX had 50% fewer Th cells in this area in both PsA and RA, but increased Th1 numbers in RA. These findings may help explain the different therapeutic responses in these diseases.

PMID:
42876702
Bibliographic data and abstract were imported from PubMed on 15 Oct 2026.

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