The Dynamic Role of the IL-33/ST2 Axis in Chronic Viral-infections: Alarming and Adjuvanting the Immune Response

Mehraj, Vikram; Ponte, Rosalie; Routy, Jean‐Pierre

doi:10.1016/j.ebiom.2016.06.047

Cited by 39 publications

(41 citation statements)

References 82 publications

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“…IL-33 is a member of the IL-1 family of cytokines constitutively expressed in the nucleus of endothelial and epithelial cells of mucosal membranes and fibroblasts and can be released in response to cell injury (26). Characterized as an alarmin, IL-33 warns the immune system of barrier injury when cells undergoing necrosis from infections or physical damage release their contents (27). In this case, the full-length active form is released and IL-33 signaling can occur.…”

Section: Discussionmentioning

confidence: 99%

Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils

Angulo

McKernan

Fichtinger

et al. 2019

Preprint

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23 24 25 2 26 ABSTRACT 27 28 Eosinophils are the prominent inflammatory cell involved in allergic asthma, atopic dermatitis, 29 eosinophilic esophagitis, and hypereosinophilic syndrome and are found in high numbers in local tissue 30 and/or circulating blood of affected patients. There is recent interest in a family of alarmins, including 31 TSLP, IL-25 and IL-33, that are epithelial-derived and released upon stimulation of epithelial cells. Several 32 genome wide association studies have found SNPs in genes encoding IL-33 to be risk factors for asthma. 33 In two studies examining the direct role of IL-33 in eosinophils, there were differences in eosinophil 34 responses. We sought to further characterize activation of eosinophils with IL-33 compared to activation 35 by other cytokines and chemokines. We assessed IL-33 stimulated adhesion, degranulation, chemotaxis 36 and cell surface protein expression in comparison to IL-3, IL-5, and eotaxin-1 on human eosinophils. Our 37 results demonstrate that IL-33 can produce as potent or more eosinophil activation than IL-3, IL-5 and 38 eotaxin-1. Thus, when considering specific cytokine targeting strategies, IL-33 will be important to 39 consider for modulating eosinophil function. 40 41 42 111 Mg 2 + and washed with 3 times with HBSS. Cells, 1x10 4 eosinophils, were added to each well along with 112 the respective cytokines (1ng/ml final concentration). After 30 min at 37°C, wells were washed 3x with 113 HBSS to remove non adherent cells. 100ul of HBSS was added to sample wells and 100ul with 1x10 4114 eosinophils were added to untreated wells to provide "Total" eosinophils for comparison. Eosinophil

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Section: Discussionmentioning

confidence: 99%

Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils

Angulo

McKernan

Fichtinger

et al. 2019

Preprint

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“…31 The "alarmin" IL-33/ST2 axis has recently been delineated to play a key role in the loss of epithelial integrity caused by microbial translocation of the mucosal barrier in mice and humans. [32][33][34][35] Despite this relevant axis, an impact of the microbiota remains a less well established and controversial risk factor for aGVHD pathogenesis. 36,37 In conclusion, this study highlights the potentially detrimental role of ATB in aGVHD severity and in OS.…”

Section: Discussionmentioning

confidence: 99%

The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation

et al. 2016

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The intestinal microbiota plays a key role in the pathogenesis of acute graft-versus-host disease (aGVHD). High-dose conditioning regimens given prior to allogeneic hematopoietic stem cell transplantation (aHSCT) modulate the composition of gut microbiota and damage the gut epithelial barrier, resulting in increased systemic inflammation. We assessed whether gut decontamination with antibiotics (ATB) prior to aHSCT influenced the frequency of aGVHD and mortality in 500 patients from two Canadian centers between 2005 and 2012. The rate of grade II-IV aGVHD was higher in the ATB arm compared with the arm without ATB (42% vs 28%; p < 0.001). This difference was mainly driven by a 2-fold higher rate of grade II-IV gastrointestinal aGVHD (GI-GVHD) in the ATB arm compared with the arm without ATB (20.7% vs 10.8%; p D 0.003). Multivariate analyses adjusted for known aGVHD risk factors revealed that more patients in the ATB group developed clinically significant GI-GVHD and liver aGVHD; adjusted odds ratio (aOR) D 1.83; p D 0.023 and aOR D 3.56; p D 0.047, respectively. Importantly, median overall survival (OS) was significantly lower in the group receiving ATB and the OS at 10 y remained decreased in the ATB group; adjusted hazard ratio (aHR) D 1.61 (p < 0.001).Without undermining the role of ATB prophylaxis to prevent infection in aHSCT, we have shown that the use of ATB that targets intestinal bacteria is associated with a more severe aGVHD that involves the GI organs and impacts OS. Prospective studies that evaluate the contribution of bacterial decontamination to aGVHD are warranted.

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“…The soluble form of the IL-33 cognate receptor, suppression of tumorogenicity (sST2), acts as a decoy receptor; the plasma concentration of sST2 is a surrogate marker of IL-33 production and a prognostic marker of sepsis, acute respiratory distress, and of heart failure [1]. Recently, we reported that sST2 plasma levels were elevated in early HIV-1 infection [2].…”

Section: Introductionmentioning

confidence: 99%

Plasma Level of Soluble ST2 in Chronically Infected HIV-1 Patients with Suppressed Viremia

Younas¹,

Psomas²,

Mehraj³

et al. 2017

TOAIDJ

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Introduction:Interleukin-33 (IL-33) is a cell damage-induced alarmin. The plasma concentration of suppression of tumorogenicity (sST2), a surrogate marker of IL-33 production, is a prognostic marker of cardiovascular disease.Observation:Recently, we reported that sST2 plasma levels were elevated in early HIV-1 infection and linked to markers of microbial translocation and of T cell activation.Results:Here we show that it is not the case in patients with suppressed viremia. Thus, IL-33 plays its alarmin role only during the early phase of the infection.

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The Dynamic Role of the IL-33/ST2 Axis in Chronic Viral-infections: Alarming and Adjuvanting the Immune Response

Cited by 39 publications

References 82 publications

Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils

Comparison of IL-33 and IL-5 Family Mediated Activation of Human Eosinophils

The influence of gut-decontamination prophylactic antibiotics on acute graft-versus-host disease and survival following allogeneic hematopoietic stem cell transplantation

Plasma Level of Soluble ST2 in Chronically Infected HIV-1 Patients with Suppressed Viremia

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