IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells

Miot, Charline; Beaumont, Élodie; Duluc, Dorothée; Guillou‐Guillemette, Hélène Le; Preisser, Laurence; Garo, Erwan; Blanchard, Simon; Fouchard, Isabelle; Créminon, Christophe; Lamourette, Patricia; Frémaux, Isabelle; Calès, Paul; Lunel‐Fabiani, Françoise; Boursier, Jérôme; Braum, Oliver; Fickenscher, Helmut; Roingeard, Philippe; Delneste, Yves; Jeannin, Pascale

doi:10.1136/gutjnl-2013-306604

Cited by 52 publications

(65 citation statements)

References 45 publications

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“…In addition to their evidence for antibacterial effects, Meller et al showed that IL-26 triggers the production of the antiviral cytokine interferon (IFN)-α (12,13) in plasmacytoid dendritic cells via activation of TLR9, by forming complexes with DNA from cells or from dying bacteria (12). Furthermore, the previous study by Miot et al also showed that IL-26 induces the production of the antiviral cytokines IFN-β and IFN-γ in NK cells in association with chronic HCV infections (7). Thus, IL-26 bears the potential to be involved in immune responses to both bacterial and viral stimulation.…”

Section: Interleukin-26 Production In Human Primary Bronchial Epithelmentioning

confidence: 91%

“…In the current study, in response to the tested viral stimuli is a strong indication of its involvement in pulmonary host defense against viral infections in the airways. This is particularly true given that IL-26 stimulates the production of antiviral cytokines including IFN-β and IFN-γ in NK cells during chronic HCV infections (7,13), as well as IFN-α in plasmacytoid dendritic cells in complex with DNA from dying bacteria and cells in vitro (12,13). Using IHC, we found a clear-cut expression of IL-26 protein in granulae and the cytoplasm of epithelial cells in bronchial tissue biopsy samples from healthy human subjects (with normal CRP levels).…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, this involvement of generic signaling molecules in the specific release of IL-26 is not only novel-it is also compelling given that these are archetype signaling pathways known to mediate a plethora of immune regulatory events in humans (40)(41)(42)(43)(44). Here, the release antiviral cytokines (IFN) (7,12,13) and is also produced by alveolar macrophages in response to a bacteria stimulus (9), the current demonstration of a viral-related response in bronchial epithelial cells suggests that IL-26 is actually produced by two critical immune barrier cells in the airways. In this way, IL-26 may contribute to pulmonary host defenses against pathogens.…”

Section: Discussionmentioning

confidence: 99%

“…Given the abundance of IL-26 protein in the human airway lumen and its referred involvement in the immune response to bacterial (9,10) and viral stimulation (7,12,13), we hypothesized that IL-26 is involved in pulmonary host defense against viruses by being produced in bronchial epithelial cells after stimulation with a viral stimulus and that this production is modulated by additional Th17 cytokines. We also hypothesized that the intracellular signaling pathways leading to IL-26 release involves mitogen-activated protein (MAP) kinases and the nuclear transcription factor NF-κB.…”

Section: Interleukin-26 Production In Human Primary Bronchial Epithelmentioning

confidence: 99%

“…Based upon these in human immunology and pathology. So far, it has been shown that IL-26 is involved in Crohn disease (5), rheumatoid arthritis (6) and chronic hepatitis C virus (HCV) infections (7), disorders that all share chronic inflammation as a common denominator. Moreover, the synovial cell production of IL-26 induces bone…”

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confidence: 99%

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Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

Fru

Kaarteenaho

Lappi‐Blanco

et al. 2017

Mol Med

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Interleukin (IL)-26 is abundant in human airways and this cytokine is involved in the local immune response to a bacterial stimulus in vivo. Specifically, local exposure to the toll-like receptor (TLR) 4 agonist endotoxin does increase IL-26 in human airways and this cytokine potentiates chemotactic responses in human neutrophils. In addition to T-helper (Th) 17 cells, alveolar macrophages can produce IL-26, but it remains unknown whether this cytokine can also be produced in the airway mucosa per se in response to a viral stimulus. Here, we evaluated whether this is the case using primary bronchial epithelial cells from the airway epithelium in vitro and explored the signaling mechanisms involved, including the modulatory effects of additional Th17 cytokines. Finally, we assessed IL-26 and its archetype signaling responses in healthy human airways in vivo. We found increased transcription and release of IL-26 protein after stimulation with the viral-related double stranded (ds) RNA polyinosinic-polycytidylic acid (poly-IC) and showed that this IL-26 release involved mitogen-activated protein (MAP) kinases and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). The release of IL-26 in response to a viral stimulus was modulated by additional Th17 cytokines. Moreover, there was transcription of IL26 mRNA and expression of the protein in epithelial cells of bronchial brush and tissue biopsies respectively after harvest in vivo. In addition, the extracellular IL-26 protein concentrations in bronchoalveolar lavage (BAL) samples did correlate with increased epithelial cell transcription of an archetype intracellular signaling molecule downstream of the IL-26-receptor complex, STAT1, in the bronchial brush biopsies. Thus, our study suggests that viral stimulation causes the production of IL-26 in lining epithelial cells of human airways, structural cells that constitute a critical immune barrier and that this production is modulated by Th17 cytokines.

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Section: Interleukin-26 Production In Human Primary Bronchial Epithelmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Interleukin-26 Production In Human Primary Bronchial Epithelmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

Fru

Kaarteenaho

Lappi‐Blanco

et al. 2017

Mol Med

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Type I and II Cytokine Superfamilies in Inflammatory Responses

Carson

Kunkel

2017

Inflammation - From Molecular and Cellular Mechanisms to the Clinic

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Organ system view of the hepatic innate immunity in HCV infection

Bang

Elmasry

Saito

2016

Journal of Medical Virology

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An orchestration of innate and adaptive immunity determines the infection outcome and whether the host achieves clearance or allows the pathogen to establish persistent infection. The robust activation of the innate immune response plays the most critical role in both limiting viral replication and halting the spread of the pathogen immediately after infection. The magnitude of innate immune activation is coupled with the efficient mounting of the adaptive immunity. Although immunity against HCV infection is known to be inadequate as most cases transitions to chronicity, approximately 25% of acute infection cases result in spontaneous clearance. The exact immune mechanisms that govern the infection outcome remain largely unknown; recent discoveries suggest that the innate immune system facilitates this event. Both infected hepatocytes and local innate immune cells trigger the front line defense program of the liver as well as the recruitment of diverse adaptive immune cells to the site of infection. Although hepatocyte is the target of HCV infection, nearly all cell types that exist in the liver are involved in the innate defense and contribute to the pathophysiology of hepatic inflammation. The main focus of this comprehensive review is to discuss the current knowledge on how each hepatic cell type contribute to the organ system level innate immunity against HCV infection as well as interplay with the viral evasion program. Furthermore, this review article also aims to synchronize the observations from both molecular biological studies and clinical studies with the ultimate goal of improving our understanding of HCV mediated hepatitis.

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IL-26 is overexpressed in chronically HCV-infected patients and enhances TRAIL-mediated cytotoxicity and interferon production by human NK cells

Abstract: This study highlights IL-26 as a new player in the inflammatory and antiviral immune responses associated with chronic HCV infection.

Cited by 52 publications

References 45 publications

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

Interleukin-26 Production in Human Primary Bronchial Epithelial Cells in Response to Viral Stimulation: Modulation by Th17 cytokines

Type I and II Cytokine Superfamilies in Inflammatory Responses

Organ system view of the hepatic innate immunity in HCV infection

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