The pro‐Th2 cytokine IL‐33 directly interacts with invariant NKT and NK cells to induce IFN‐γ production

Bourgeois, Elvire Anne; Pham, Linh; Samson, Michel; Diem, Séverine; Barra, Anne; Roga, Stéphane; Gombert, Jean‐Marc; Schneider, Elke; Dy, Michel; Gourdy, Pierre; Girard, Jean-Philippe; Herbelin, André

doi:10.1002/eji.200838575

Cited by 298 publications

(264 citation statements)

References 26 publications

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“…IL-33 polarizes naive T cells to produce Th2-associated cytokines IL-4, IL-5 and IL-13 [7] and functions as a chemoattractant for Th2 cells in vitro and in vivo [12], but also induces secretion of proinflammatory cytokines and chemokines by mast cells [13], basophils [14] and Th1 type cytokines from NK and NKT cells [14,15]. Also, IL-33 amplifies polarization of alternatively activated M2 macro-phages [16], induces maturation of dendritic cells [17] and may promote Th1-type response [18].…”

Section: Introductionmentioning

confidence: 99%

Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis

et al. 2013

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To assess the role of interleukin (IL)-33 and ST2, the receptor for IL-33, in the pathogenesis of systemic juvenile idiopathic arthritis (s-JIA), we sequentially measured the serum levels of IL-33 and soluble ST2 (sST2) in patients with s-JIA and determined their correlation with measures of disease activity and severity. Twenty-four patients with s-JIA, 5 with rheumatoid factor positive polyarticular JIA (RF + poly-JIA), and 20 age-matched healthy controls (HCs) were analyzed. IL-33 and sST2 levels were quantified in serum by enzyme-linked immunosorbent assays. Serum IL-33 levels in most patients with active s-JIA were below the lowest detection limit. Serum IL-33 levels in patients with RF + poly-JIA were significantly higher than those in patients with s-JIA and HC. Serum sST2 levels in patients during the active phase of s-JIA were much higher than those in patients with poly-JIA and HC. Serum sST2 levels in patients with s-JIA were significantly elevated even in the inactive phase, when other clinical parameters were normalized. Serum sST2 levels correlated positively with the clinical parameters of disease activity. These findings indicate that ST2 may be an important mediator in s-JIA. Serum sST2 levels in patients with s-JIA correlated with disease activity, suggesting a potential role as a promising indicator of disease activity.

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Section: Introductionmentioning

confidence: 99%

Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis

et al. 2013

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“…This strategy is of pathophysiological relevance, considering the well-established role played by iNKT cells during allergic asthma together with the fact that they are effectively targeted and functionally modified by 21].…”

Section: Introductionmentioning

confidence: 99%

A natural protective function of invariant NKT cells in a mouse model of innate‐cell‐driven lung inflammation

et al. 2011

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Activation of invariant natural killer T (iNKT) cells by treatment with their a-galactosylceramide ligand provides therapeutic benefits in several immune inflammatory settings. Given the artificial nature of this stimulation, the natural regulatory functions of iNKT remain uncertain. Addressing this issue in a mouse model of innate-cell-driven lung inflammation induced by the cytokine/alarmin IL-33 that targets iNKT cells, we found that eosinophil and neutrophil recruitment was markedly increased in treated iNKT cell-deficient (Ja18 KO) mice, as was the local production of eotaxin and keratinocyte chemoattractant chemokines. By contrast, lung inflammation decreased after adoptive transfer of iNKT cells, which restored the WT inflammatory response in Ja18 KO mice. Finally, we established that this natural anti-inflammatory function of iNKT cells depends on their IFN-c production and on endogenous IL-12. Our study provides the first evidence of a protective role of iNKT cells during lung inflammation that does not require pharmacological TCR engagement.Keywords: IL-33 . Inflammation . iNKT cells . Innate cells Supporting Information available online IntroductionInvariant natural killer T (iNKT) cells constitute a population of T cells, which share some characteristics with NK cells. In this regard, they occupy a strategic position between adaptive and innate immunity. iNKT cells are characterized by the expression of an invariant Va14Ja18 antigen receptor, chiefly paired with Vb8.2 in mice and of the invariant Va24Ja18/Vb11 pair in humans (for reviews see [1,2] Frontline key regulatory functions, based on the therapeutic benefits provided by their specific exogenous ligand a-galactosyl ceramide (a-GC) in several models of autoimmunity and allergic asthma (for reviews see [5][6]) [7][8][9][10][11]. However, whether these cells actually play a regulatory role in these pathologies in the absence of pharmacological TCR engagement is still doubtful (for reviews see [6]). The answer to this fundamental question in iNKT cell biology has remained elusive since almost all pathological experimental models of autoimmunity and asthma require an immunization phase that presumably recruits and activates iNKT cells in a non-physiological rather than a disease-specific manner. Hence, there is still no definite evidence that iNKT cells specifically exert natural regulatory functions in the experimental allergic OVA-or ragweed-induced asthma model, in which iNKT cells can promote disease protection [10,11] or induction and/or exacerbation [12][13][14], depending on their mode of activation.Here, we used a novel approach to address this issue in a model of innate-cell-driven lung inflammation induced by , a cytokine that has recently been described as a member of the IL-1 family [16] and credited with alarmin functions [17][18][19]. This strategy is of pathophysiological relevance, considering the well-established role played by iNKT cells during allergic asthma together with the fact that they are effectively targeted and functiona...

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“…20 IL-33 (IL-33/IL-1F11/NF-HEV) is a member of the IL-1 family of cytokines. 21,22 IL-33 exerts its biological function by binding to the ST2 receptor on the surface of T-helper 2 (Th2) cells, 22 mast cells, 22,23 basophils, 24 eosinophils, 25 NKT cells, 26 dendritic cells, 27 and neutrophils. 28 Similar to the effects of UV, IL-33 has potent immunemodulating properties that are mediated by the induction of cytokines including IL-1, -4, -6, -10. and -13, as well as chemokines such as CXCL8, CCL2, CCL3, and CCL5.…”

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confidence: 99%

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

Byrne

Beaugie

O’Sullivan

et al. 2011

The American Journal of Pathology

101

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The cellular and molecular mechanisms by which UV radiation modulates inflammation and immunity while simultaneously maintaining skin homeostasis is complex and not completely understood. Similar to the effects of UV, IL-33 has potent immune-modulating properties that are mediated by the downstream induction of cytokines and chemokines. We have discovered that exposure of mice in vivo or human skin samples ex vivo to inflammatory doses of UVB induced IL-33 expression within the epidermal and dermal skin layers. Using a combination of murine cell lines and primary human cells, we demonstrate that both UV and the oxidized lipid platelet activating factor induce IL-33 expression in keratinocytes and dermal fibroblasts. Highlighting the significance of these results, we found that administering IL-33 to mice in vivo suppressed the induction of Th1-mediated contact hypersensitivity responses. This may have consequences for skin cancer growth because UV-induced squamous cell carcinomas that evade immunological destruction were found to express significantly higher levels of IL-33. Finally, we demonstrate that dermal mast cells and skininfiltrating neutrophils closely associate with UV-induced IL-33-expressing fibroblasts. Our results therefore identify and support a role for IL-33 as an important early danger signal produced in response to inflammation-inducing UV radiation.

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The pro‐Th2 cytokine IL‐33 directly interacts with invariant NKT and NK cells to induce IFN‐γ production

Cited by 298 publications

References 26 publications

Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis

Soluble ST2 as a marker of disease activity in systemic juvenile idiopathic arthritis

A natural protective function of invariant NKT cells in a mouse model of innate‐cell‐driven lung inflammation

The Immune-Modulating Cytokine and Endogenous Alarmin Interleukin-33 Is Upregulated in Skin Exposed to Inflammatory UVB Radiation

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