Preferential Accumulation of Activated Th1 Cells Not Only in Rheumatoid Arthritis But Also in Osteoarthritis Joints

Yamada, Hisakata; Nakashima, Yasuharu; Okazaki, Ken; Mawatari, Taro; Fukushi, Jun Ichi; Oyamada, Akiko; Fujimura, Kenjiro; Iwamoto, Yukihide; Yoshikai, Yasunobu

doi:10.3899/jrheum.101355

Cited by 50 publications

(58 citation statements)

References 37 publications

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“…T cells may reflect disease activity status in RA patients. In addition, similar to the data of recent studies [13,26], our results showed that the percentages of circulating IL-17-positive cells in CD4?CD161? T cells were significantly higher than the percentages in CD4?…”

Section: Discussionsupporting

confidence: 93%

Frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells correlate with disease activity in rheumatoid arthritis

et al. 2013

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OBJECTIVE: Rheumatoid arthritis (RA) is a common autoimmune disease that is primarily driven by effector T cells, particularly Th17 cells, which are mainly contained within CD4+CD161+ T cells. Thus, we aimed to explore whether the frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were correlated with RA disease activity. METHODS: The surface phenotype and cytokine production of blood were analyzed by flow cytometry in 52 RA patients and 17 healthy controls. The disease activity was evaluated by the 28-joint disease activity score. RESULTS: The frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells were increased in RA patients, and they were elevated in patients with active disease status compared to patients with low disease status. Furthermore, their frequencies were positively correlated with disease activity parameters. Receiver operating characteristic curve analysis revealed that IL-17-producing CD4+CD161+ T cell levels were able to distinguish disease activity with 60.7 % sensitivity and 87.5 % specificity, while CD4+CD161+ T cell levels showed 92.9 % sensitivity and 66.7 % specificity. CONCLUSION: These results support the hypothesis that Th17 cells are involved in the pathogenesis of RA and suggest that circulating CD4+CD161+ T cells are a potential biomarker of RA disease activity.

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Section: Discussionsupporting

confidence: 93%

Frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells correlate with disease activity in rheumatoid arthritis

et al. 2013

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“…The present study also identified higher levels of INF-γ and IL-17 in OA patients. These results are consistent with those of previous studies, which indicated that OA was a T-helper cell 1 (Th1)-mediated form of arthritis (25). Yamada et al (25) and Lùrati et al (26) reported elevated levels of Th17 cells in OA patients, which further illustrated OA as a disease marked by an imbalance in the immune response towards a pro-inflammatory state.…”

Section: Discussionsupporting

confidence: 93%

Increased frequency of peripheral blood follicular helper T cells and elevated serum IL-21 levels in patients with knee osteoarthritis

Shan

Liu

et al. 2017

Molecular Medicine Reports

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An aberrant immune response has been implicated in the pathogenesis of osteoarthritis (OA). However, the role of peripheral blood follicular helper T (TFH) cells in the pathogenesis of OA has yet to be elucidated. The purpose of the present study was to examine the role of TFH cells and serum interleukin-21 (IL-21) in the pathogenesis of OA. Frequency of peripheral blood inducible costimulator (ICOS)+, programmed death 1 (PD-1)+, and IL-21+ CXCR5+CD4+ T cells in 40 patients with OA and 13 healthy controls (HCs) were examined by flow cytometry. The disease state in individual patients was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Concentrations of serum IL-21, interferon-γ (INF-γ), IL-4, IL-17A, and C-reactive protein (CRP) were determined, and the erythrocyte sedimentation rate (ESR) was measured. The percentages of CXCR5+CD4+ cells, PD-1+CXCR5+CD4+, ICOS+CXCR5+CD4+ and IL-21+CXCR5+CD4+ T cells in OA patients were significantly higher than those in the HCs. Furthermore, serum IL-21, IL-17A and IFN-γ levels in OA patients were significantly higher than those in HCs. Expression of IL-21+TFH cells in OA patients demonstrated a positive correlation with OA disease activity, CRP levels and WOMAC. TFH cells and IL-21 appear to serve an important role in the progression of OA. IL-21+TFH cells may prove to be a marker of OA disease activity.

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“…Immune cells are the major ‘disease effector’ cell types in AIDs and previous studies have reported a critical role for T-cell differentiation and enrichment of causal genes for Th1 and Th2 pathways [52-55]. Since data on lncRNA genes are lacking, we investigated the expression levels of AID locus-encoded genes in seven circulating immune cell subsets and in four cell types during CD4 + T-cell differentiation using the RNA-sequencing data.…”

Section: Resultsmentioning

confidence: 99%

Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity

et al. 2014

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BackgroundAlthough genome-wide association studies (GWAS) have identified hundreds of variants associated with a risk for autoimmune and immune-related disorders (AID), our understanding of the disease mechanisms is still limited. In particular, more than 90% of the risk variants lie in non-coding regions, and almost 10% of these map to long non-coding RNA transcripts (lncRNAs). lncRNAs are known to show more cell-type specificity than protein-coding genes.MethodsWe aimed to characterize lncRNAs and protein-coding genes located in loci associated with nine AIDs which have been well-defined by Immunochip analysis and by transcriptome analysis across seven populations of peripheral blood leukocytes (granulocytes, monocytes, natural killer (NK) cells, B cells, memory T cells, naive CD4+ and naive CD8+ T cells) and four populations of cord blood-derived T-helper cells (precursor, primary, and polarized (Th1, Th2) T-helper cells).ResultsWe show that lncRNAs mapping to loci shared between AID are significantly enriched in immune cell types compared to lncRNAs from the whole genome (α <0.005). We were not able to prioritize single cell types relevant for specific diseases, but we observed five different cell types enriched (α <0.005) in five AID (NK cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, and psoriasis; memory T and CD8+ T cells in juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis; Th0 and Th2 cells for inflammatory bowel disease, juvenile idiopathic arthritis, primary biliary cirrhosis, psoriasis, and rheumatoid arthritis). Furthermore, we show that co-expression analyses of lncRNAs and protein-coding genes can predict the signaling pathways in which these AID-associated lncRNAs are involved.ConclusionsThe observed enrichment of lncRNA transcripts in AID loci implies lncRNAs play an important role in AID etiology and suggests that lncRNA genes should be studied in more detail to interpret GWAS findings correctly. The co-expression results strongly support a model in which the lncRNA and protein-coding genes function together in the same pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-014-0088-0) contains supplementary material, which is available to authorized users.

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Preferential Accumulation of Activated Th1 Cells Not Only in Rheumatoid Arthritis But Also in Osteoarthritis Joints

Abstract: There was a quantitative but not qualitative difference in CD4 T cells, including the expression of activation markers and cytokine profiles, between RA and OA joints.

Cited by 50 publications

References 37 publications

Frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells correlate with disease activity in rheumatoid arthritis

Frequencies of circulating IL-17-producing CD4+CD161+ T cells and CD4+CD161+ T cells correlate with disease activity in rheumatoid arthritis

Increased frequency of peripheral blood follicular helper T cells and elevated serum IL-21 levels in patients with knee osteoarthritis

Expression profiles of long non-coding RNAs located in autoimmune disease-associated regions reveal immune cell-type specificity

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