New immune cells in spondyloarthritis: Key players or innocent bystanders?

Venken, Koen; Elewaut, Dirk

doi:10.1016/j.berh.2016.02.002

Cited by 17 publications

(17 citation statements)

References 85 publications

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“…Spondyloarthritis are a cluster of inflammatory conditions which share clinical genetic and pathophysiological characteristics [29]. It is worth noting that an overexpression of A 3 ARs was previously found in peripheral blood mononuclear cells derived from patients with RA, psoriasis and Crohn’s disease compared with healthy subjects [30].…”

Section: Discussionmentioning

confidence: 99%

Role and Function of A2A and A3 Adenosine Receptors in Patients with Ankylosing Spondylitis, Psoriatic Arthritis and Rheumatoid Arthritis

Ravani

Vincenzi

Bortoluzzi

et al. 2017

IJMS

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Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are chronic inflammatory rheumatic diseases that affect joints, causing debilitating pain and disability. Adenosine receptors (ARs) play a key role in the mechanism of inflammation, and the activation of A2A and A3AR subtypes is often associated with a reduction of the inflammatory status. The aim of this study was to investigate the involvement of ARs in patients suffering from early-RA (ERA), RA, AS and PsA. Messenger RNA (mRNA) analysis and saturation binding experiments indicated an upregulation of A2A and A3ARs in lymphocytes obtained from patients when compared with healthy subjects. A2A and A3AR agonists inhibited nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) activation and reduced inflammatory cytokines release, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6. Moreover, A2A and A3AR activation mediated a reduction of metalloproteinases (MMP)-1 and MMP-3. The effect of the agonists was abrogated by selective antagonists demonstrating the direct involvement of these receptor subtypes. Taken together, these data confirmed the involvement of ARs in chronic autoimmune rheumatic diseases highlighting the possibility to exploit A2A and A3ARs as therapeutic targets, with the aim to limit the inflammatory responses usually associated with RA, AS and PsA.

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Section: Discussionmentioning

confidence: 99%

Role and Function of A2A and A3 Adenosine Receptors in Patients with Ankylosing Spondylitis, Psoriatic Arthritis and Rheumatoid Arthritis

Ravani

Vincenzi

Bortoluzzi

et al. 2017

IJMS

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“…Since salt drives IL-23R expression, another question is the specific cells that could be sensitive to this environmental factor. Most experimental studies focussed the analysis on T lymphocytes, but IL-17A can be release by a wide range of other cells than Th17, including ILC3 and MAIT cells (Venken and Elewaut, 2015 ). These 2 cellular subsets are present in the gut, and thus, may be responsive to a salt diet.…”

Section: Discussionmentioning

confidence: 99%

“…“Typical” or “conventional” Th17 cells have been described as a main—but not the only—cellular population responsible for IL-17 production. Indeed, a large variety of innate and adaptive immune cells are responsible for IL-17A and IL-17F production, including CD8 + T cells, CD4 − /CD8 − α/β T lymphocytes, γ/δ T cells, NK cells, NKT cells, neutrophils, innate lymphoid cells (ILC), and especially ILC3 cells, and mucosal-associated invariant T (MAIT) cells (Venken and Elewaut, 2015 ). The differentiation of naive CD4 + T cells toward the Th17 subset involves the expression of the specific retinoic acid receptor- related orphan receptor γ-T (RORγt) transcription factor (Ivanov et al, 2006 ).…”

Section: The Il-23/th17 Pathway Il-17 and Th17 Cells: Implication Inmentioning

confidence: 99%

Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overview of the Experimental and Clinical Evidence

et al. 2018

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Immune mediated diseases (IMDs) are complex chronic inflammatory diseases involving genetic and environmental factors. Salt intake has been proposed as a diet factor that can influence the immune response. Indeed, experimental data report the influence of sodium chloride on the differentiation of naive CD4+ T cells into IL-17 secreting T helper (Th) cells (Th17 cells), by a mechanism involving the serum glucocorticoid kinase-1 (SGK1) that promotes the expression of the IL-23 receptor (IL-23R). The IL-23/IL-23R is critical for pathogenic inflammatory Th17 cell differentiation. Experimental data in murine models of arthritis, colitis and encephalomyelitis corroborate these findings. This manuscript reviews the current knowledge on the effects of sodium chloride on innate and adaptive immunity. We also performed a systematic literature review for clinical studies examining the relationships between salt consumption and the development or the activity/severity of the most common IMDs mediated by the IL-23/Th17 pathway, i.e., rheumatoid arthritis (RA), multiple sclerosis (MS), and Crohn's disease (CD). Nine studies were found, 4 in RA, 4 in MS and 1 in CD. An association was found between developments of anti-citrullinated protein antibody (ACPA) positive RA in smokers and salt intake, but these results were not confirmed in another study. For MS, no association was observed in pediatric subjects while in adult patients, a link was found between salt intake and disease activity. However, this result was not confirmed in another study. These conflicting results highlight the fact that further evaluation in human IMDs is required. Moreover, physicians need to develop clinical trials with diet interventions to evaluate the impact of low salt intake on disease activity/severity of IMDs.

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“…After lining up the usual and a few unusual suspects, it seems that although strong arguments point toward an important contribution of the IL-23/IL-17 axis mediating SpA, it still remains difficult to pinpoint which of the above-described cell types are major players ( 132 ). Overall, recent studies collectively favor innate and innate-like immune cell involvement rather than adaptive T cells ( 6 , 31 , 32 ).…”

Section: Concluding Remarks: Whodunit?mentioning

confidence: 99%

Whodunit? The Contribution of Interleukin (IL)-17/IL-22-Producing γδ T Cells, αβ T Cells, and Innate Lymphoid Cells to the Pathogenesis of Spondyloarthritis

Reinhardt

Prinz

2018

Front. Immunol.

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γδ T cells, αβ T cells, and innate lymphoid cells (ILCs) are capable of producing interleukin (IL)-17A, IL-17F, and IL-22. Among these three families of lymphocytes, it is emerging that γδ T cells are, at least in rodents, the main source of these key pro-inflammatory cytokines. γδ T cells were implicated in multiple inflammatory and autoimmune diseases, including psoriasis, experimental autoimmune encephalomyelitis and uveitis, colitis, and rheumatoid arthritis. Recent findings pointed toward a central role of γδ T cells in the pathogenesis of spondyloarthritis (SpA), a group of inflammatory rheumatic diseases affecting the axial skeleton. SpA primarily manifests as inflammation and new bone formation at the entheses, which are connecting tendons or ligaments with bone. In SpA patients, joint inflammation is frequently accompanied by extra-articular manifestations, such as inflammatory bowel disease or psoriasis. In humans, genome-wide association studies could link the IL-23/IL-17 cytokine axis to SpA. Accordingly, antibodies targeting IL-23/IL-17 for SpA treatment already showed promising results in clinical studies. However, the contribution of IL-17-producing γδ T cells to SpA pathogenesis is certainly not an open-and-shut case. Indeed, the cell types that are chiefly involved in local inflammation in human SpA still remain largely unclear. Some studies focusing on blood or synovium from SpA patients reported augmented IL-17-producing and IL-23 receptor-expressing γδ T cells, but other cell types might contribute as well. Here, we summarize the current understanding of how γδ T cells, αβ T cells, and ILCs contribute to the pathogenesis of human and experimental SpA.

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New immune cells in spondyloarthritis: Key players or innocent bystanders?

Cited by 17 publications

References 85 publications

Role and Function of A2A and A3 Adenosine Receptors in Patients with Ankylosing Spondylitis, Psoriatic Arthritis and Rheumatoid Arthritis

Role and Function of A2A and A3 Adenosine Receptors in Patients with Ankylosing Spondylitis, Psoriatic Arthritis and Rheumatoid Arthritis

Could Sodium Chloride be an Environmental Trigger for Immune-Mediated Diseases? An Overview of the Experimental and Clinical Evidence

Whodunit? The Contribution of Interleukin (IL)-17/IL-22-Producing γδ T Cells, αβ T Cells, and Innate Lymphoid Cells to the Pathogenesis of Spondyloarthritis

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