T cells form distinct spatially restricted immune responses in synovium of patients with psoriasis arthritis and rheumatoid arthritis
4 affiliations
- 1Institute of Clinical Pharmacology, Goethe University Frankfurt , ,
- 2Department of Rheumatology, Hospital Clínic and Fundació de Recerca Clinic-Barcelona-Institut d’Investigacions Biomèdiques August Pi i sunyer (IDIBAPS) , ,
- 3Fraunhofer Institute for Translational Medicine and Pharmacology ITMP , ,
- 4Division of Rheumatology and Clinical Immunology, Università Cattolica del Sacro Cuore, Fondazione Policlinico Universitario Agostino Gemelli IRCCS , ,
Abstract
Introduction: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
Related
- Regulatory T cell dysfunction and therapeutic advances in rheumatoid arthritis, psoriasis, vitiligo, and systemic lupus erythematosus
- Spatially restricted bmp16 in an extra-embryonic syncytium promotes dorsoventral patterning
- Joint–brain communication in rheumatoid arthritis: glial mechanisms, pain phenotypes, and translational evidence
- Histone lactylation in fibroblast-like synoviocytes drives CXCL1-mediated immune cell recruitment in rheumatoid arthritis
- Serum Calprotectin as predictor of Rheumatoid Arthritis disease severity and Mortality
BibTeX
@article{behr2026cells,
title = {{T cells form distinct spatially restricted immune responses in synovium of patients with psoriasis arthritis and rheumatoid arthritis}},
author = {Nathalie J. Behr and Julio Ramírez and Ana B. Azuaga and Raquel Celis and Gerd Geisslinger and Frank Behrens and Stefano Alivernini and Juan D. Cañete and Klaus Scholich},
journal = {Frontiers in immunology},
year = {2026},
month = sep,
doi = {10.3389/fimmu.2026.1946638},
url = {https://europepmc.org/article/PMC/PMC13661973},
note = {CC BY},
}
RIS
TY - JOUR
TI - T cells form distinct spatially restricted immune responses in synovium of patients with psoriasis arthritis and rheumatoid arthritis
AU - Nathalie J. Behr
AU - Julio Ramírez
AU - Ana B. Azuaga
AU - Raquel Celis
AU - Gerd Geisslinger
AU - Frank Behrens
AU - Stefano Alivernini
AU - Juan D. Cañete
AU - Klaus Scholich
PY - 2026
DA - 2026/09/30
JO - Frontiers in immunology
DO - 10.3389/fimmu.2026.1946638
UR - https://europepmc.org/article/PMC/PMC13661973
AB - Introduction: 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. Methods: 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. Results: 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. Conclusions: 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.
SN - 1664-3224
ER -