Th17-Inducing Conditions Lead to<i>in vitro</i>Activation of Both Th17 and Th1 Responses in Behcet’s Disease

Deniz, Rabia; Virlan, Aysın Tulunay; Özdemir, Filiz; Ünal, Ali; Özen, Gülşen; Alıbaz-Öner, Fatma; Aydin-Tatli, Imren; Mumcu, Gonca; Ergun, Tülin; Direşkeneli, Haner

doi:10.1080/08820139.2017.1306865

Cited by 31 publications

(25 citation statements)

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“…Our finding of an increased frequency of Th17 cells and their increased expression of proinflammatory cytokines in patients with active BD uveitis confirms previous studies that suggest a significant role of Th17 immune responses in BD. [12][13][14][15][16][17][18] We also observed an increase in the expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 by peripheral blood CD4 þ T cells and monocytes during an acute attack of BD uveitis. Follow-up investigations after interferon alfa-2a treatment, which resulted in clinical remission of uveitis in 70.4% of the patients, revealed resolution of pathologic adaptive and innate immune system responses that included induction of IL-10 expression by Treg cells, suppression of Th17 cells, and reduced expression of TLRs on CD4 þ T cells and monocytes.…”

Section: Discussionmentioning

confidence: 69%

“…7 Although scarce, studies focusing on the frequency of Treg cells in the peripheral blood show controversial results in patients with BD uveitis. [8][9][10][11] Recent studies documented the relative abundance and central role of T helper (Th) 17 cells and their plasticity by increased expression of IL-17, a key proinflammatory cytokine of T helper 17 (Th17) pathway, and IFN-c. [12][13][14][15][16][17][18] Neutrophildominant inflammatory lesions in BD are also possibly driven by Th17 immune responses. 12 Patients with active BD, especially those with uveitis or folliculitis, were reported to have a significantly higher Th17/Th1 cell ratio in peripheral blood than healthy controls.…”

mentioning

confidence: 99%

“…[8][9][10][11] Recent studies documented the relative abundance and central role of T helper (Th) 17 cells and their plasticity by increased expression of IL-17, a key proinflammatory cytokine of T helper 17 (Th17) pathway, and IFN-c. [12][13][14][15][16][17][18] Neutrophildominant inflammatory lesions in BD are also possibly driven by Th17 immune responses. 12 Patients with active BD, especially those with uveitis or folliculitis, were reported to have a significantly higher Th17/Th1 cell ratio in peripheral blood than healthy controls. 19 A study showed that Th17 cells from patients with active BD uveitis exposed to the TNF-a inhibitor infliximab in vitro failed to produce IL-17 and showed diminished expression of the Th17 transcription factor, RARrelated orphan receptor (ROR)ct, suggesting that TNF-a plays a role in Th17 differentiation.…”

mentioning

confidence: 99%

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Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behçet Disease Uveitis

Albayrak

Oray

Can

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To investigate the effect of interferon alfa-2a on T regulatory (Treg) cells, T helper 17 (Th17) cells, and expression of Toll-like receptors (TLRs) in Behçet disease (BD) patients with uveitis. METHODS. Twenty-seven patients who received interferon alfa-2a for active BD uveitis despite conventional immunomodulatory therapies and healthy controls were enrolled. Peripheral blood Treg and Th17 cell frequencies were determined by flow cytometry as gated cells for CD3 þ CD4 þ Foxp3 þ and CD3 þ CD4 þ IL17A þ , respectively. Th17 RAR-related orphan receptor (ROR)ct mRNA expression was verified by real-time PCR (RT-PCR). Treg and Th17 cell cytokines were detected by ELISA in the supernatant of short-term cell cultures. RT-PCR was used to assess expression of TLR-2, TLR-3, TLR-4, TLR-8, and TLR-9 using cDNA prepared from CD4 þ T cells and monocytes. RESULTS. Treg and Th17 cell frequencies and Th17 RORct expression were significantly elevated, and IL-10 concentration in Treg cell supernatants was significantly lower in BD patients than in controls. Th17 IL-17, IL-6, IL-21, IL-22, IL-23, IFN-c, and TNF-a concentrations were significantly higher and all TLR expressions were significantly elevated in patients. Interferon alfa-2a led to a significant reversal in Treg and Th17 cell frequencies, Th17 RORct expression, Treg and Th17 cell cytokine production, and TLR expression by CD4 þ T cells and monocytes. CONCLUSIONS. Despite a relative increase in Treg cells, impaired IL-10 production suggests that Treg dysfunction may play a role in induction of BD uveitis. Favorable effects of interferon alfa-2a may be associated with recovery of Treg cell function, suppression of Th17 cells, and reduced expression of TLRs on CD4 þ T cells and monocytes.

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Section: Discussionmentioning

confidence: 69%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behçet Disease Uveitis

Albayrak

Oray

Can

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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“…BD lesions in their early stages are predominated by neutrophils which are major immunoregulatory cell group of the innate immune system. Another member of innate immunity, natural killer (NK) cells are also found in BD lesions (67).…”

Section: Immunitymentioning

confidence: 99%

Behçet’s Disease: An Overview of Etiopathogenesis

2019

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Behçet's disease (BD) is a systemic inflammatory disease with a chronic, relapsing-remitting course of unknown etiology hallmarked predominantly by mucocutaneous lesions and ocular involvement. BD shares some common features with autoimmune and autoinflammatory diseases and spondyloarthropathies (MHC-I-opathies). It is related to more than one pathogenic pathway triggered by environmental factors such as infectious agents in genetically predisposed subjects. The interplay between genetic background and immune system is linked to the BD presentation. Genetic factors have been investigated extensively, and several recent genome-wide association studies have confirmed HLA-B * 51 to be the strongest genetic susceptibility factor. However, new non-HLA susceptibility genes have been identified. Genetic variations in the genes encoding the cytokines could affect their function and be associated with disease susceptibility. Infectious agents such as Streptococcus sanguinis or the differences in salivary or gut microbiome composition can be considered to trigger the innate-derived inflammation, which is, subsequently, sustained by adaptive immune responses. Altered trimming of microbial and/or endogenous peptides by endoplasmic reticulum aminopeptidase 1 (ERAP1), presented by HLA-B * 51 , may play a key role in BD pathogenesis causing an alteration in T cell balance with downregulation of Tregs and expansion of Th1 and Th17. The activity of neutrophils is increased and there is an intense neutrophil infiltration in the early stage of inflammation in organs affected by the disease. Association with HLA-B * 51 and increased IL-17 response seems to have an important role in neutrophil activity. In this paper, we provide an overview of the most recent advances on BD etiopathogenesis.

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“…Deniz et al [33] reported that under Th17-stimulating conditions, T cells express both IL-17 and IFN-γ in BD. In addition, they speculated that more prominent IL-17 and IFN-γ production by all lymphocyte subsets in BD may be associated with the increased innate responses, early tissue neutrophil infiltrations, and late adaptive immunity in BD.…”

Section: Circulating Th17 Cell Frequencies Are Correlated With Diseasmentioning

confidence: 99%

The Role of Th17 Cells in the Pathogenesis of Behçet’s Disease

Nanke¹,

Kotake²

2020

Different Aspects of Behçet's Disease

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Behçet's disease (BD) is a polysymptomatic and recurrent systemic vasculitis with a chronic course and unknown cause. BD is now categorized as both autoimmune diseases and auto inflammatory diseases. The pathogenesis of BD is still unclear; however, BD has been thought as a Th1-related disease, with elevating levels of Th1 cytokines such as IFN-γ, TNF-α, and IL-2. Some investigators found that Th17-associated cytokines were elevated in patients with BD; thus, IL-17/IL-23 pathway and Th17 cells may have crucial roles in the pathogenesis of BD. In this chapter, we review the pathogenic role of Th17 cells in BD.

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Th17-Inducing Conditions Lead toin vitroActivation of Both Th17 and Th1 Responses in Behcet’s Disease

Cited by 31 publications

References 14 publications

Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behçet Disease Uveitis

Effect of Interferon alfa-2a Treatment on Adaptive and Innate Immune Systems in Patients With Behçet Disease Uveitis

Behçet’s Disease: An Overview of Etiopathogenesis

The Role of Th17 Cells in the Pathogenesis of Behçet’s Disease

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