Decreased Gene Expression of Epstein–Barr Virus-Induced Gene 3 (EBI-3) may Contribute to the Pathogenesis of Rheumatoid Arthritis

Iranshahi, Nasrin; Assar, Shirin; Amiri, Samira; Zafari, Parisa; Fekri, Adel; Taghadosi, Mahdi

doi:10.1080/08820139.2018.1549066

Cited by 33 publications

(18 citation statements)

References 37 publications

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“…Ultimately, of 98 articles screened, 15 studies met the eligibility criteria. [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31] The characteristics of the included studies are described in Table 1, and the study selection process is given in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

“…Twenty‐three studies have been selected for full‐text analysis; after securitization of them, eight studies were excluded due to the lack of sufficient data or similar results that were also reported in other publications. Ultimately, of 98 articles screened, 15 studies met the eligibility criteria 17–31 . The characteristics of the included studies are described in Table 1, and the study selection process is given in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

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Neopterin serum level does not reflect the disease activity in rheumatoid arthritis: A systematic review and meta‐analysis

et al. 2020

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Rheumatoid arthritis (RA) is a chronic autoimmune disease caused by established chronic inflammation. Neopterin levels have extensively been considered as a marker of immune activation during inflammation. In this study, we performed a systematic evaluation and meta-analysis to elucidate the overall relationship between neopterin concentration and RA disease activity. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines, a systematic review was conducted using PubMed, Google Scholar, Web of Science, and Scopus from 2000 to August 2020. The Newcastle-Ottawa scale was used to assess the quality of eligible studies. The effect size (ES) and corresponding 95% confidence intervals (CIs) were calculated to evaluate this association. A total of 15 studies out of 98 met our inclusion criteria. The pooled analysis found that patients with RA had high level of neopterin; however, no statistically significant association was found between neopterin levels with high, intermediate, and low diseases activity score (DAS)-28 (ES =11.18, 95% CI: 6.02 to 16.34, and I 2 = 91.8%; and ES = 8.57, 95% CI: 6.41 to 10.37, and I 2 = 99.5%; and ES =12.45, 95% CI: −1.68 to 26.58, and I 2 = 99.0%, respectively). Our results indicated that the neopterin concentration does not seem to have any substantial impact on the RA disease activity.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Neopterin serum level does not reflect the disease activity in rheumatoid arthritis: A systematic review and meta‐analysis

et al. 2020

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“…Why the latter occurs remains to be investigated and explained. Given that as a self-standing molecule EBI3 has been, for example, involved in the pathogenesis of rheumatoid arthritis, 48 inflammatory bowel disease, 49 systemic sclerosis, 12 and cardiac inflammation, 50 as well in growth-promoting activity of lung 51 breast, 52 and colorectal cancer, 53…”

Section: Discussionmentioning

confidence: 99%

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39

Cassatella

Gardiman

Arruda‐Silva

et al. 2020

Journal of Leukocyte Biology

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The IL-12 family of cytokines plays crucial functions in innate and adaptive immunity. These cytokines include heterodimers sharing distinct (IL-12A, IL-23A, and IL-27A) with two (IL-12B and Epstein-Barr virus induced gene 3 [EBI3]) chains, respectively, IL-12 (IL-12B plus IL-12A) and IL-23 (IL-12B plus IL-23A) sharing IL-12B, IL-27 (EBI3 plus IL-27A), IL-35 (EBI3 plus IL-12A), and IL-39 (EBI3 plus IL-23A) sharing EBI3. In this context, we have recently reported that highly pure neutrophils incubated with TLR8 agonists produce functional IL-23. Previously, we showed that neutrophils incubated with LPS plus IFN for 20 h produce IL-12. Herein, we investigated whether highly pure, TLR8-activated, neutrophils produce EBI3, and in turn IL-27, IL-35, and IL-39, the IL-12 members containing it. We report that neutrophils incubated with TLR8 ligands, TNF and, to a lesser extent, LPS, produce and release remarkable amounts of EBI3, but not IL-27A, consequently excluding the possibility for an IL-27 production. We also report a series of unsuccessful experiments performed to investigate whether neutrophil-derived EBI3 associates with IL-23A to form IL-39. Furthermore, we show that neutrophils incubated with IFN in combination with either TLR8 or TLR4 ligands express/produce neither IL-12, nor IL-35, due to the inability of IFN , contrary to previous findings, to activate IL12A transcription. Even IL-27 was undetectable in supernatants harvested from IFN plus R848-treated neutrophils, although they were found to accumulate IL27A transcripts. Finally, by immunohistochemistry experiments, EBI3-positive neutrophils were found in discrete pathologies only, including diverticulitis, cholecystitis, Gorham disease, and Bartonella Henselae infection, implying a specific role of neutrophil-derived EBI3 in vivo.

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“…Previous studies have shown that IL‐35 is an important inhibitor of autoimmune inflammation and that it can inhibit the osteoclast formation and bone loss induced by TNF‐α during the process of RA 27,28 . In addition, a decrease in the serum levels of the EBI3 subunit of IL‐35 has been detected in RA patients, which may cause an insufficient IL‐35 response 29 . Moreover, the serum levels of IL‐35 have been demonstrated to be negatively associated with the active status and Disease Activity Score of 28 joints (DAS28) scores in RA patients, suggesting that IL‐35 inhibits the pathogenesis of RA.…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Interleukin‐35 regulates the balance of Th17 and Treg responses during the pathogenesis of connective tissue diseases

Wang

Lei

2020

Int J of Rheum Dis

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Interleukin (IL)-35 belongs to the IL-12 cytokine family and is a heterodimer of the p35 and Epstein-Barr virus-induced gene 3 (EBI3) subunits. Functionally, IL-35 can promote the proliferation and activation of regulatory T cells (Tregs) and suppress the function of T helper 17 (Th17) cells and other inflammatory cells to inhibit immune responses. In recent years, an abnormal IL-35 expression causing a Th17/Treg imbalance has been associated with the development and progression of several connective tissue diseases (CTDs), such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM)/polymyositis (PM), and primary Sjögren's syndrome (pSS). Here, we review the role of IL-35 in regulating the balance of Th17/Treg responses in different types of CTDs and provide new insights into the role of IL-35 in these diseases.

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Decreased Gene Expression of Epstein–Barr Virus-Induced Gene 3 (EBI-3) may Contribute to the Pathogenesis of Rheumatoid Arthritis

Cited by 33 publications

References 37 publications

Neopterin serum level does not reflect the disease activity in rheumatoid arthritis: A systematic review and meta‐analysis

Neopterin serum level does not reflect the disease activity in rheumatoid arthritis: A systematic review and meta‐analysis

Human neutrophils activated by TLR8 agonists, with or without IFNγ, synthesize and release EBI3, but not IL-12, IL-27, IL-35, or IL-39

Interleukin‐35 regulates the balance of Th17 and Treg responses during the pathogenesis of connective tissue diseases

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