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Positive feedback between cDC1s and CD8+ T cells typifies the inflammation of HLA-B27+ arthritis

ABSTRACT: Enthesitis-related arthritis (ERA) is a subtype of juvenile idiopathic arthritis (JIA) with enthesitis and sacroiliitis, which differ from other types of JIA in symptoms, pathogenesis, and outcome. Although the association of human leukocyte antigen-B27 (HLA-B27) with ERA has been confirmed for decades, the pathogenesis of ERA is poorly understood. Here, we performed single-cell RNA-seq of 1,73,134 mononuclear cells extricated from patients with oligoarthritis (OligoA) or ERA and integrated 58,725 PBMCs of healthy people to profile the immune characteristic that discriminates ERA from OligoA. We found that conventional type 1 dendritic cells (cDC1s) were enriched in the joints of patients with ERA and exhibited a high level of MHC class I antigen presentation. Central memory CD8+ T cells critically contributed to the elevation of XCL1, recruiting XCR1+ cDC1 in joints of ERA. Flow cytometry and enzyme-linked immunosorbent assay (ELISA) analyses confirmed an increased proportion and interaction of cDC1s and CD8+ T cells. In addition, macrophages occupied the causal position in the pathogenesis of OligoA, along with high expression of MHC class II molecules on macrophages and cDC2s in the joints. This study suggests that the positive feedback between cDC1s and CD8+ T cells is a key mediator of HLA-B27-positive arthritis pathogenesis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE213095 | GEO | 2026/02/22

REPOSITORIES: GEO

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Project description:Objective: A multi-center study of recent onset juvenile idiopathic arthritis (JIA) subjects prior to treatment with DMARDS or biologics was undertaken to identify peripheral blood gene expression differences between JIA subclasses and controls. Methods: PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays. Results: 9,501 differentially expressed probe sets were identified among JIA subtypes and controls (ANOVA, FDR 5%). Specifically, 193, 1036, 873 and 7595 probe sets were different between controls and ERA, persistent oligoarthritis, RF- polyarthritis and systemic JIA samples respectively. In persistent oligoarthritis, RF- polyarthritis and systemic JIA subtypes, up-regulation of gene associated with IL-10 signaling was prominent. A hemoglobin cluster was identified that was under-expressed in ERA patients but over-expressed in systemic JIA. The influence of JAK/STAT, ERK/MAPK, IL-2 and B cell receptor signaling pathways was evident in persistent oligoarthritis. In systemic JIA, up regulation of innate immune pathways, including IL-6, TLR/IL1R, and PPAR signaling were noted, along with down regulation of gene networks related to NK and T cells. Complement and coagulation pathways were up-regulated in systemic JIA with a subset of these components differentially-expressed in the other three subtypes. Conclusions: Expression analysis identified differentially expressed genes in PBMCs between subclasses of JIA early in disease and controls, thus providing evidence for immunobiologic differences between these forms of childhood arthritis. Keywords: Gene expression. PBMC. Patients compared with controls. PBMC from 59 healthy children and 136 JIA subjects (28 enthesitis-related arthritis[ERA], 42 persistent oligoarthritis, 45 RF- polyarthritis, and 21 systemic) were isolated on Ficoll. Poly-A RNA was labeled using NuGEN Ovation and gene expression profiles were obtained using Affymetrix HG-U133 plus 2.0 Arrays

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Positive feedback between cDC1s and CD8+ T cells typifies the inflammation of HLA-B27+ arthritis

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