Full Papers
Dynamics of interleukin-23/interleukin-17 axis and type 1 regulatory T cells across disease stages in axial spondyloarthritis
J. Yeo1, M.-G. Kim2, S.Y. Heo3, Y. Yang4, M.R. Seo5, H.-J. Choi6, Y. Jung7, E.Y. Lee8, H.J. Baek9
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea.
- Interdisciplinary Program in Cancer Biology, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon, Republic of Korea.
- Department of Microbiology, College of Medicine, Gachon University, Incheon; Lee Gil Ya Cancer and Diabetes Institute, Gachon University, Incheon; and Department of Health Science and Technology, Gachon Advanced Institute for Health Science & Technology, Gachon University, Incheon, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Seoul National University Hospital, Seoul; and Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Republic of Korea.
- Division of Rheumatology, Department of Internal Medicine, Gil Medical Center, Gachon University College of Medicine, Incheon; and Department of Internal Medicine, Pyeongchang Health Center and County Hospital, Gangwon State, Republic of Korea. baekhj429@googlemail.com
CER19156
Full Papers
PMID: 41758549 [PubMed]
Received: 28/07/2025
Accepted : 04/02/2026
In Press: 27/02/2026
Abstract
OBJECTIVES:
The interleukin (IL)-23/IL-17 pathway is central to the pathogenesis of axial spondyloarthritis (axSpA); however, treatments targeting IL-23 have shown inconsistent effectiveness across spondyloarthritis subtypes. We hypothesised that the IL-23/IL-17 axis varies with disease stage and is modulated by its regulatory counterparts, such as type 1 regulatory T (Tr1) cells.
METHODS:
Serum levels of IL-17A and IL-23, along with peripheral CD4+IL-17A+ cells, monocytes (CD14+HLA-DR+), dendritic cells (DCs, CD11c+HLA-DR+), and Tr1 cells (CD4+CD49b+LAG3+FoxP3-IL-10+), were analysed in 20 patients with non-radiographic axSpA (nr-axSpA) and 24 with radiographic axSpA (r-axSpA) using enzyme-linked immunosorbent assay and flow cytometry. Additionally, we assessed IL-17A production by healthy CD4+ T cells stimulated by monocyte-derived DCs (moDCs) from patients with axSpA through co-culture experiments.
RESULTS:
Patients with nr-axSpA had higher serum IL-23 levels (p=0.014), whereas IL-17A levels were comparable between both groups (p=0.912). Peripheral DCs from the nr-axSpA group produced more IL-23 (p=0.010), while no significant differences were observed in Th17 cell proportions (p>0.05). MoDCs from patients with nr-axSpA induced higher pro-inflammatory cytokine production in healthy CD4+ T cells than those from patients with r-axSpA (p<0.05). Notably, Tr1 cells were reduced in the nr-axSpA group (p=0.025), and IL-10 selectively suppressed IL-23 production by nr-axSpA moDCs (p=0.236).
CONCLUSIONS:
These findings indicate that IL-23-associated immune activity may be relatively more prominent in early axSpA and that differences in Tr1 cell-related regulation across disease stages could contribute to this pattern.
