Dataset Information

Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis.

ABSTRACT:

Objectives

The aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.

Methods

The study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene expression was estimated by qPCR, and the serum cytokine levels were determined by ELISA.

Results

The percentage of Treg (CD4+CD25highCD127-) cells in RA patients was lower than in OA patients or HCs. Proportions of Th17 (CD4+CCR6+CXCR3-) cells were higher in RA and OA in comparison to HCs. STAT5 showed a very high expression in the blood of RA patients compared to healthy subjects. The expression of STAT5 and HELIOS was not detected in Th17 cells. A positive correlation between SMAD3 and STAT3 in RA patients was observed. Negative correlations between HIF-1A and SMAD2 in RA Treg cells and DAS-28 score were observed. The range of serum of IL-17 and IL-21 were higher in RA patients than in OA patients. Concentrations of serum IL-2 and IFN-? were higher in RA and OA patients than in healthy subjects. Based on the ROC analysis, the diagnostic potential of the combination of HIF1A, SMAD3 and STAT3, was determined at AUC 0.95 for distinguishing RA patients from HCs. For distinguishing RA patients from OA patients the diagnostic potential of the combination of SMAD2, SMAD3, SMAD4 and STAT3, was determined at AUC 0.95.

Conclusion

Based on our study, we conclude that SMAD3 and STAT3 could be potential diagnostic biomarkers for RA.

SUBMITTER: Paradowska-Gorycka A

PROVIDER: S-EPMC7759671 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Publications

Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis.

Paradowska-Gorycka Agnieszka A Wajda Anna A Romanowska-Próchnicka Katarzyna K Walczuk Ewa E Kuca-Warnawin Ewa E Kmiolek Tomasz T Stypinska Barbara B Rzeszotarska Ewa E Majewski Dominik D Jagodzinski Pawel Piotr PP Pawlik Andrzej A

Frontiers in immunology 20201211

<h4>Objectives</h4>The aim of our study was to determine whether there is a correlation between transcription factors expression and Th17/Treg ratio, cytokine profile in the RA phenotype as well as to identify transcription factors that could be a potential biomarker for RA.<h4>Methods</h4>The study was conducted on 45 patients with RA, 27 patients with OA and 46 healthy controls (HCs). Th17 and Treg frequency was determined by flow cytometry (15 patients with RA/OA and 15 subjects of HC). Gene ...[more]

PMID: 33362761

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Project description:IntroductionRheumatoid arthritis (RA) is a chronic inflammatory disease involving a variety of immune cells, including adaptive T and B cells and innate lymphoid cells (ILCs). Understanding the pathogenic role of these immune cells in RA provides new insights into the intervention and treatment of RA.MethodsA total of 86 patients with RA (RA group) and 50 healthy controls (HC) were included in the study. The immune cells of CD4+, CD19+ B, NK, Th17, Treg, ILCs, and their subsets (i.e., ILC1s, ILC2s, and ILC3s) were characterized in peripheral blood mononuclear cells by flow cytometry. Cytokines (i.e., IFN-γ, IL-4, IL-10, IL-17A, IL-22, and IL-33) in sera were detected using ELISA. The above immune cells and cytokines were analyzed in patients with different disease activity status and positive ( +) or negative ( -) rheumatoid factor (RF)/anti-citrullinated protein antibodies (ACPA).ResultsPatients with RA had higher percentages of CD4+ T, CD19+ B, Th17, ILC2s, and ILC3s and lower percentages of Treg and ILC1s than HC. Patients with RA had elevated levels of IFN-γ, IL-4, IL-17A, and IL-22 and decreased level of IL-10. Compared with HC, patients with high disease activity had higher percentages of Th17, ILC2s, and ILC3s; lower percentages of ILC1s; and lower level of IL-10. The percentage of Treg cells in remission, low, moderate, and high disease activities decreased, whereas the level of IL-17A increased compared with HC. Furthermore, RF+ or ACPA+ patients exhibited elevated percentages of CD19+ B, ILC2s, and ILC3s and had decreased percentage of ILC1s and Treg cells than HC. The percentage of Th17 cells increased in RF-/ACPA- and RF+/ACPA+ patients. However, the above immune cells between RF or ACPA positive and negative patients were not significantly different.ConclusionTh17, Treg, and ILC subset dysregulations are present in patients with RA but may not be associated with conventionally defined seropositive RF and ACPA. Key Points • Th17, Treg, and ILC subset dysregulations are present in patients with RA but may reflect inflammation rather than specific diseases and stages. • No difference for the distribution of Th17, Treg, and ILC subsets between RF+ and RF- patients and between ACPA+ and ACPA- patients. The screening spectrum of RF and ACPA serology should be expanded to elucidate the role of immune cells in RA pathogenesis.

Project description:Interleukin-26 (IL-26), a member of the IL-10 cytokine family, induces the production of proinflammatory cytokines by epithelial cells. IL-26 has been also reported overexpressed in Crohn's disease, suggesting that it may be involved in the physiopathology of chronic inflammatory disorders. Here, we have analyzed the expression and role of IL-26 in rheumatoid arthritis (RA), a chronic inflammatory disorder characterized by joint synovial inflammation. We report that the concentrations of IL-26 are higher in the serums of RA patients than of healthy subjects and dramatically elevated in RA synovial fluids compared to RA serums. Immunohistochemistry reveals that synoviolin(+) fibroblast-like synoviocytes and CD68(+) macrophage-like synoviocytes are the main IL-26-producing cells in RA joints. Fibroblast-like synoviocytes from RA patients constitutively produce IL-26 and this production is upregulated by IL-1-beta and IL-17A. We have therefore investigated the role of IL-26 in the inflammatory process. Results show that IL-26 induces the production of the proinflammatory cytokines IL-1-beta, IL-6, and tumor necrosis factor (TNF)-alpha by human monocytes and also upregulates the expression of numerous chemokines (mainly CCL20). Interestingly, IL-26-stimulated monocytes selectively promote the generation of RORgamma t(+) Th17 cells, through IL-1-beta secretion by monocytes. More precisely, IL-26-stimulated monocytes switch non-Th17 committed (IL-23R(-) or CCR6(-) CD161(-)) CD4(+) memory T cells into Th17 cells. Finally, synovial fluids from RA patients also induce Th17 cell generation and this effect is reduced after IL-26 depletion. These findings show that IL-26 is constitutively produced by RA synoviocytes, induces proinflammatory cytokine secretion by myeloid cells, and favors Th17 cell generation. IL-26 thereby appears as a novel proinflammatory cytokine, located upstream of the proinflammatory cascade, that may constitute a promising target to treat RA and chronic inflammatory disorders.

Dataset Information

Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis.

Objectives

Methods

Results

Conclusion

Publications

Th17/Treg-Related Transcriptional Factor Expression and Cytokine Profile in Patients With Rheumatoid Arthritis.

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