Type-III interferons and rheumatoid arthritis: Correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels

Castillo‐Martínez, Diana; Juarez, Maribel; Patlán, Mariana; Páez, Araceli; Massó, Felipe; Amezcua-Guerra, Luís M.

doi:10.1080/08916934.2017.1289181

Cited by 14 publications

(5 citation statements)

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“…Type III interferons (IFN-III or IFN-λ) are also produced by pDCs and promote upregulation of genes normally associated with response to IFN-I ( 54 , 62 , 63 ). Furthermore, IFN-III are increased in RA and can associate with disease-specific antibodies ( 64 , 65 ). However, pDCs had comparable IFN-I and IFN-III transcript levels to those in other circulating lymphocyte subsets, and these levels were independent of the background IGS.…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis

et al. 2018

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ObjectiveDendritic cells (DCs) are key orchestrators of immune function. To date, rheumatoid arthritis (RA) researchers have predominantly focused on a potential pathogenic role for CD1c+ DCs. In contrast, CD141+ DCs and plasmacytoid DCs (pDCs) have not been systematically examined, at least in early RA. In established RA, the role of pDCs is ambiguous and, since disease duration and treatment both impact RA pathophysiology, we examined pDCs, and CD1c+ and CD141+ conventional DCs (cDCs), in early, drug-naïve RA (eRA) patients.MethodsWe analyzed the frequency and phenotype of pDCs, CD1c+, and CD141+ DCs from eRA patients and compared findings with healthy controls. In parallel, we performed transcriptional analysis of >600 immunology-related genes (Nanostring) from peripheral blood pDCs, CD1c+ DCs, B cells, T cells, and monocytes.ResultsAll DC subsets were reduced in eRA (n = 44) compared with healthy controls (n = 30) and, for pDCs, this was most marked in seropositive patients. CD141+ and CD1c+ DCs, but not pDCs, had a comparatively activated phenotype at baseline (increased CD86) and CD1c+ DC frequency inversely associated with disease activity. All DC frequencies remained static 12 months after initiation of immunomodulatory therapy despite a fall in activation markers (e.g., HLA-DR, CD40). There was no association between the whole blood interferon gene signature (IGS) and pDC or CD1c+ DC parameters but an inverse association between CD141+ DC frequency and IGS was noted. Furthermore, IFN-I and IFN-III mRNA transcripts were comparable between eRA pDC and other leukocyte subsets (B cells, CD4+, and CD8+ T cells and monocytes) with no obvious circulating cellular source of IFN-I or IFN-III. Transcriptomic analysis suggested increased pDC and CD1c+ DC proliferation in eRA; pDC differentially expressed genes also suggested enhanced tolerogenic function, whereas for CD1c+ DCs, pro-inflammatory transcripts were upregulated.DiscussionThis is the first detailed examination of DC subsets in eRA peripheral blood. Compared with CD1c+ DCs, pDCs are less activated and may be skewed toward tolerogenic functions. CD141+ DCs may be implicated in RA pathophysiology. Our findings justify further investigation of early RA DC biology.

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Section: Discussionmentioning

confidence: 99%

Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis

et al. 2018

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“…Lv et al 20 found that serum IL-28B levels were significantly lower in RA group than in control group, and speculated that IL-28B may be stimulated by inflammation of joint, may move to the joint cavity to decrease the production of some inflammatory factors including IL-1b, TNF-a and IL-17 and inhibit neutrophil migration to reduce the destruction and inflammation of joint. Furthermore, Castillo-Martinez et al 23 found that IL-28A levels were higher in RA patients with active disease than HCs. Combined with our results, IL-28A and IL-28B expressions in AS patients may have different changes in inflammatory environments.…”

Section: Discussionmentioning

confidence: 98%

Changes in Serum Levels of Type-III Interferons in Ankylosing Spondylitis Treated With Tumor Necrosis Factor-Alpha Inhibitors

Jiao

Chang

2019

Arch Rheumatol

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Objectives:This study aims to determine the changes in serum levels of type-III interferons (type-III IFNs) in ankylosing spondylitis (AS) patients treated with tumor necrosis factor-alpha inhibitors (TNFi) and analyze the correlations between serum type-III IFN levels and disease activity. Patients and methods:The study included 57 AS patients (51 males, 6 females; mean age 29.7±7.0 years; range, 18 to 50 years), who had been diagnosed with AS and had active disease before the start of the study (median disease duration: four years, range 1.3 to 8.0 years). Control group included 50 healthy, age-and sex-matched individuals (45 males, 5 females; mean age 25.5±6.7 years; range, 18 to 55 years). The enzyme-linked immunosorbent assay was used to assess the serum interleukin (IL)-29, IL-28A, and IL-28B levels of AS patients at baseline and first, third, sixth months after treatment with TNFi. Clinical and laboratory features of the disease were also evaluated for AS patients at baseline and first, third, sixth months after treatment. Results: Serum IL-28A levels were significantly higher in AS patients (354.8±164.0 pg/mL) than in controls (257.2±99.6, p=0.003) at baseline. Serum IL-28B levels were significantly lower in AS patients (median, 491.4 pg/mL, range 296.6 to 944.6 pg/mL) than in controls (1121.1±409.3 pg/mL, p=0.000) at baseline. Serum IL-29 levels at third month after treatment (median 430.9, range 277.4 to 1023.9 pg/mL) were significantly increased compared with baseline (median 399.1, range 261.2 to 826.7 pg/mL), p=0.002) and controls (335.2±100.5 pg/mL, p=0.041). There was no association between serum type-III IFN levels and disease activity indexes at baseline. Serum levels of IL-28A were negatively correlated with erythrocyte sedimentation rate levels at first and sixth months after treatment (r=-0.266, p=0.046; r=-0.286, p=0.034, respectively). Serum levels of IL-28A were negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index at third month after treatment (r=-0.269, p=0.043). Serum levels of IL-29 were negatively correlated with Bath Ankylosing Spondylitis Disease Activity Index at third month after treatment (r=-0.299, p=0.024). There was a significant increasing trend for serum IL-28B after TNFi treatment in AS patients, opposite to the decreasing trend for disease activity. Conclusion: These findings indicate that type-III IFNs may be involved in the pathogenesis of AS. Thus, type-III IFNs may provide new targets for the treatment of AS.

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“…In a murine model of TLR7-induced lupus, IFNL promotes immune dysregulation through expansion of myeloid and T cell populations in the spleen and blood and induction of chemokine production by keratinocytes (24). Furthermore, IFNL protein levels are upregulated in patients with rheumatoid arthritis (42)(43)(44)(45) and contribute to inflammation and cartilage degradation during osteoarthritis (25). Studies of allergic airway disease, vaccination induced inflammation, and in vitro models examining T cell subtypes reveal the ability of IFNL to inhibit Th2 polarization (26)(27)(28)46) and promote IFNγ production (15,27,28,47), indicating that IFNL may enhance Th1 function (48).…”

Section: Discussionmentioning

confidence: 99%

Targeting interferon-_λ signaling promotes recovery from central nervous system autoimmunity

Manivasagam

et al. 2021

Preprint

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Type III interferons (IFNLs) are newly discovered cytokines, acting at epithelial and other barriers, that exert immunomodulatory functions in addition to their primary roles in antiviral defense. Here we define a role for IFNLs in maintaining autoreactive T cell effector function and limiting recovery in a murine model of multiple sclerosis (MS), experimental autoimmune encephalomyelitis (EAE). Genetic or antibody-based neutralization of the IFNL receptor (IFNLR) resulted in lack of disease maintenance during EAE, with loss of CNS Th1 effector responses and limited axonal injury. Phenotypic effects of IFNLR signaling were traced to increased antigen presenting cell (APC) function, with associated increase in T cell production of IFNγ and GM-CSF. Consistent with this, IFNL levels within lesions of CNS tissues derived from MS patients were elevated compared to MS normal appearing white matter (NAWM). Furthermore, expression of IFNLR was selectively elevated in MS active lesions compared to inactive lesions or NAWM. These findings suggest IFNL signaling as a potential therapeutic target to prevent chronic autoimmune neuroinflammation.

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Type-III interferons and rheumatoid arthritis: Correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels

Abstract: Serum IFNλ1 and IFNλ2 levels are abnormally elevated in patients with RA and the former are linearly associated with circulating anti-MCV antibody levels. These results may place type-III IFN as an attractive new therapeutic target in RA.

Cited by 14 publications

References 14 publications

Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis

Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis

Changes in Serum Levels of Type-III Interferons in Ankylosing Spondylitis Treated With Tumor Necrosis Factor-Alpha Inhibitors

Targeting interferon-_λ signaling promotes recovery from central nervous system autoimmunity

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Type-III interferons and rheumatoid arthritis: Correlation between interferon lambda 1 (interleukin 29) and antimutated citrullinated vimentin antibody levels

Abstract: Serum IFNλ1 and IFNλ2 levels are abnormally elevated in patients with RA and the former are linearly associated with circulating anti-MCV antibody levels. These results may place type-III IFN as an attractive new therapeutic target in RA.

Cited by 14 publications

References 14 publications

Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis

Phenotypic and Transcriptomic Analysis of Peripheral Blood Plasmacytoid and Conventional Dendritic Cells in Early Drug Naïve Rheumatoid Arthritis

Changes in Serum Levels of Type-III Interferons in Ankylosing Spondylitis Treated With Tumor Necrosis Factor-Alpha Inhibitors

Targeting interferon-λ signaling promotes recovery from central nervous system autoimmunity

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Product

Resources

About

Targeting interferon-_λ signaling promotes recovery from central nervous system autoimmunity