Expression of Th1 and Th2  Immunoregulatory Cytokines  by Human Eosinophils

Woerly, G.; Roger, Nadine; Loiseau, Sylvie; Capron, Moníque

doi:10.1159/000024038

Cited by 68 publications

(44 citation statements)

References 7 publications

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“…This result suggests that other non-CD4 + non-CD8 + T cells may be the source of this increase (e.g. contamination with granulocytes, detected evenly on day 14 pi by flow cytometry [15,32]). As on day 7 pi, the CD8 + IL10 + population was absent on day 14 pi, whereas the frequency of CD4 + IL10 + cells had increased further.…”

Section: Discussionmentioning

confidence: 92%

Early hepatic immune response in rats infected with Fasciola hepatica

et al. 2002

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-We investigated the phenotype of the T cells (CD4 + and CD8 + ) that produced Th1 (IFN-γ ) and Th2 cytokines (IL-4 and IL-10) during the first two weeks of experimental fasciolosis in rats. We also followed the kinetics of the cytokine and proliferative responses of hepatic mononuclear cells (HMNC) over the same period. We found that HMNC were more numerous in the infected animals than in the controls. The percentage of CD4 + cells increased significantly after infection, whereas the percentage of CD8 + cells did not change. Moreover, the frequency of the cells producing (CP) cytokine changed after infection. The frequency of CP IFN-γ on 7 days postinfection (pi) was similar to that in control animals. However, the frequency of CP IFN-γ was clearly lower on day 14 pi, whereas the frequency of CP IL-4 and CP IL-10 had increased. The CP IL-10-were mostly CD4 + . Mitogenic stimulation (phorbol myristate acetate/ionomycin) of HMNC led to an increase in the amounts of the Th2 cytokines in the supernatant on days 7 and 14 pi, with the increase more pronounced on day 14. In contrast, IFN-γ levels also increased by day 7 pi but then decreased to below control levels by day 14. In addition, HMNC proliferation in response to mitogen followed a similar pattern to IFN-γ production. These findings suggested that, during the first 2 weeks of infection, F. hepatica induced a transient Th0 cytokine profile followed by downregulation of the cellular response and the induction of a Th2 cytokine profile.Fasciola hepatica / rat / cytokine / liver / lymphocytes Résumé -Réponse immunitaire hépatique précoce chez le rat infesté par Fasciola hepatica. Nous avons caractérisé le phénotype des sous-populations lymphocytaires T (CD4 + , CD8 + ) qui produisent des cytokines de type Th1 (IFN-γ ) et Th2 (IL-4, IL-10) au cours de l'infestation expérimen-tale par F. hepatica chez le rat (phase précoce). Nous avons aussi suivi la production des cytokines et (33) 2 47 42 77 74; e-mail: sibille@tours.inra.fr la réponse proliférative des cellules mononucléaires hépatiques (CMNH) après une stimulation in vitro par des mitogènes (phorbol myristate acetate) et par des antigènes spécifiques (les produits d'excrétion-sécrétion de F. hepatica). Le pourcentage des cellules CD4 + augmente après infestation tandis que celui des cellules CD8 + demeure inchangé. Après infestation, la fréquence des cellules productrices (CP) de cytokine change. Tandis qu'au 7 e jour après infestation (JAI) la fréquence des CP d'IFN-γ reste identique à celles des animaux témoins, elle est nettement plus basse au 14 e JAI ; la fréquence des CP d'IL-4 et des CP d'IL-10 augmente (surtout les CD4 + IL-10 + , notamment au 14 e JAI). En outre, dans les surnageants de culture des CMNH, la production de cytokines de type Th2 est accrue au 7 e JAI et plus importante encore au 14 e JAI. Le niveau de production d'IFN-γ augmente au 7 e JAI mais décroît jusqu'à devenir inférieure à celle du témoin au 14 e JAI. De plus, la ré-ponse proliférative est plus importante au 7 e JAI mais...

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Section: Discussionmentioning

confidence: 92%

Early hepatic immune response in rats infected with Fasciola hepatica

et al. 2002

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“…Activated eosinophils are one of the primary sources of cytotoxic proteins, proinflammatory cytokines, and growth factors, such as IL‐4, IL‐5, IL‐10, and IL‐13 6, and promote numerous immunoregulatory functions that lead to the progression of inflammation, mucus secretion, tissue remodeling, and angiogenesis 7.…”

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confidence: 99%

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Frei

Luschnig

Parzmair

et al. 2016

Allergy

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BackgroundAccumulation of activated eosinophils in tissue is a hallmark of allergic inflammation. The endocannabinoid 2‐arachidonoylglycerol (2‐AG) has been proposed to elicit eosinophil migration in a CB 2 receptor/Gi/o‐dependent manner. However, it has been claimed recently that this process may also involve other mechanisms such as cytokine priming and the metabolism of 2‐AG into eicosanoids. Here, we explored the direct contribution of specific CB 2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo.Methods In vitro studies including CB 2 expression, adhesion and migratory responsiveness, respiratory burst, degranulation, and calcium mobilization were conducted in human peripheral blood eosinophils and mouse bone marrow‐derived eosinophils. Allergic airway inflammation was assessed in mouse models of acute OVA‐induced asthma and directed eosinophil migration.Results CB 2 expression was significantly higher in eosinophils from symptomatic allergic donors. The selective CB 2 receptor agonist JWH‐133 induced a moderate migratory response in eosinophils. However, short‐term exposure to JWH‐133 potently enhanced chemoattractant‐induced eosinophil shape change, chemotaxis, CD11b surface expression, and adhesion as well as production of reactive oxygen species. Receptor specificity of the observed effects was confirmed in eosinophils from CB 2 knockout mice and by using the selective CB 2 antagonist SR144528. Of note, systemic application of JWH‐133 clearly primed eosinophil‐directed migration in vivo and aggravated both AHR and eosinophil influx into the airways in a CB 2‐specific manner. This effect was completely absent in eosinophil‐deficient ∆dblGATA mice.ConclusionOur data indicate that CB 2 may directly contribute to the pathogenesis of eosinophil‐driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB 2‐mediated priming of eosinophils. Hence, antagonism of CB 2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.

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“…E osinophils are important effector cells in allergic diseases, particularly in late-phase reactions, because they release bronchoconstrictor mediators such as leukotriene C 4 and other chemoattractants that cause further influx of inflammatory cells into the tissue (1). Eosinophils produce proinflammatory cytokines and growth factors, including immunoregulatory Th2-type cytokines (2)(3)(4).…”

mentioning

confidence: 99%

“…Eosinophils produce proinflammatory cytokines and growth factors, including immunoregulatory Th2-type cytokines (2)(3)(4). Mucosal damage in asthma is associated with cytotoxic mediators that are released by activated eosinophils, and it has been shown that asthmatic patients who received treatment based on eosinophil counts in sputum had significantly fewer severe asthma exacerbations than patients treated according to standard management therapy (5).…”

mentioning

confidence: 99%

Prostaglandin E2 Inhibits Eosinophil Trafficking through E-Prostanoid 2 Receptors

Sturm

Schratl

Schuligoi

et al. 2008

The Journal of Immunology

108

110

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The accumulation of eosinophils in lung tissue is a hallmark of asthma, and it is believed that eosinophils play a crucial pathogenic role in allergic inflammation. Prostaglandin (PG) E2 exerts anti-inflammatory and bronchoprotective mechanisms in asthma, but the underlying mechanisms have remained unclear. In this study we show that PGE2 potently inhibits the chemotaxis of purified human eosinophils toward eotaxin, PGD2, and C5a. Activated monocytes similarly attenuated eosinophil migration, and this was reversed after pretreatment of the monocytes with a cyclooxygenase inhibitor. The selective E-prostanoid (EP) 2 receptor agonist butaprost mimicked the inhibitory effect of PGE2 on eosinophil migration, whereas an EP2 antagonist completely prevented this effect. Butaprost, and also PGE2, inhibited the C5a-induced degranulation of eosinophils. Moreover, selective kinase inhibitors revealed that the inhibitory effect of PGE2 on eosinophil migration depended upon activation of PI3K and protein kinase C, but not cAMP. In animal models, the EP2 agonist butaprost inhibited the rapid mobilization of eosinophils from bone marrow of the in situ perfused guinea pig hind limb and prevented the allergen-induced bronchial accumulation of eosinophils in OVA-sensitized mice. Immunostaining showed that human eosinophils express EP2 receptors and that EP2 receptor expression in the murine lungs is prominent in airway epithelium and, after allergen challenge, in peribronchial infiltrating leukocytes. In summary, these data show that EP2 receptor agonists potently inhibit eosinophil trafficking and activation and might hence be a useful therapeutic option in eosinophilic diseases.

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Expression of Th1 and Th2 Immunoregulatory Cytokines by Human Eosinophils

Cited by 68 publications

References 7 publications

Early hepatic immune response in rats infected with Fasciola hepatica

Early hepatic immune response in rats infected with Fasciola hepatica

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen‐induced pulmonary inflammation in mice

Prostaglandin E2 Inhibits Eosinophil Trafficking through E-Prostanoid 2 Receptors

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