Hierarchical suppression of asthma-like responses by mucosal tolerance

Keller, Alexandre C.; Mucida, Daniel; Gomes, E. A.; Faquim-Mauro, Eliana L.; Faria, Ana Maria Caetano; Rodríguez, Dunia; Russo, Marco

doi:10.1016/j.jaci.2005.10.019

Cited by 49 publications

(62 citation statements)

References 21 publications

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“…Indeed, previous studies have demonstrated that short-term or continuous intranasal exposure of mite allergen, but not of OVA, caused eosinophilia in BAL fluid and bronchoconstriction in BALB/c mice, along with elevated Th2-cell-associated production of antibodies in serum and Th2-cell-associated production of cytokines by splenocytes (28,49), whereas other studies have demonstrated that repeated exposure of BALB/c mice to an inhaled low dose of OVA inhibited the potential to develop a specific Th2 response in the periphery due to a noncompartmentalized induced immune tolerance (5,44). In a recent study, the prevention of a cellular and a humoral Th2-mediated allergic response was obtained by intranasal administration of three consecutive high doses of OVA (100 g), whereas lower doses (10 g) were found to be less effective and intranasal treatment was less effective than orally induced tolerance (29). Thus, our results suggest that BLG shares the same tolerogenic properties as OVA when it is administered intranasally before sensitization.…”

Section: Discussionmentioning

confidence: 99%

“…As examples, intranasal application of recombinant birch allergen Bet v1 led to the suppression of the allergic immune response in sensitized mice (56), and continuous intranasal exposure to OVA in sensitized BALB/c animals led to the complete abrogation of airway inflammation (53). However, the effectiveness of mucosal OVA administration in suppressing T-cell immunity declined when mucosal antigen delivery started after immunization and became selective for the Th2-mediated pulmonary allergic response but not for T-cell-mediated antibody production (29). The Th1 adjuvant effect of L. lactis BLG and L. lactis IL-12 should then be of great interest in controlling the ongoing Th2 response in our model.…”

Section: Discussionmentioning

confidence: 99%

“…In order to improve the immunomodulatory effect of L. lactis BLG on allergen sensitization and on the elicitation of the allergic reaction, we investigated the effect of the prophylactic coadministration of L. lactis BLG and L. lactis IL-12 in a mouse model of allergy (2). So far, as contradictory results have been reported with ovalbumin (OVA) and house dust mite allergens after intranasal administration (tolerance versus sensitization) (28,29), we also investigated the effect of intranasal administration of BLG as a protein either alone or coadministered with the IL-12 protein.…”

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Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice

Cortes-Perez

Ah‐Leung

Bermúdez‐Humarán

et al. 2007

Clin Vaccine Immunol

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The Th1/Th2 balance deregulation toward a Th2 immune response plays a central role in allergy. We previously demonstrated that administration of recombinant Lactococcus lactis strains expressing bovine ␤-lactoglobulin (BLG), a major cow's milk allergen, partially prevents mice from sensitization. In the present study, we aimed to improve this preventive effect by coadministration of L. lactis BLG and a second recombinant L. lactis strain producing biologically active interleukin-12 (IL-12). This L. lactis strain producing IL-12 was previously used to enhance the Food allergies, i.e., immediate-type, immunoglobulin E (IgE)-mediated immune responses, affect 2 to 2.5% of the general populations of Western countries (22,24,25). It results from the activation of the Th2-type helper lymphocytes. In mice, this response is mainly characterized by the production of interleukin-4 (IL-4) and IL-13, which induce the production of IgE and IgG1, and of IL-5, which attracts eosinophils. In contrast, the Th1 response is characterized by the induction of gamma interferon (IFN-␥) and IL-2 production and the stimulation of cellular immunity. Th1 and Th2 cells regulate their own development via the cytokines produced: IFN-␥ suppresses Th2-cell proliferation and promotes Th1-cell proliferation, whereas IL-4 promotes additional Th2-cell proliferation and inhibits Th1-cell development (39,43,45).A recent study suggests that an early allergen-specific induction of Th1 cells before allergy sensitization could not efficiently prevent the development of atopic disorders: Th1 priming was abolished in the presence of allergen-specific Th2 cells, whereas Th1 cells could not inhibit subsequent priming of Th2 cells (58). The use of adjuvants that increase the proliferation of Th1 cells and that render them more efficient in inhibiting Th2 cells would therefore be of great interest in the management of allergic diseases. These observations prompted us to explore the adjuvant effect of IL-12 in a mouse model of allergic reaction to bovine ␤-lactoglobulin (BLG), a major milk allergen (2). IL-12 is a heterodimeric cytokine produced by antigen-presenting cells that promotes the development of naïve Th cells into Th1 effector cells and that induces IFN-␥ production (51,52,54). IL-12 also inhibits Th2 class switching by repression of the IL-4 cytokine (15,17,46,54,55). Moreover, treatment with recombinant IL-12 has been shown to have positive effects on bronchial hyperresponsiveness and the eosinophilic response (11). Unfortunately, despite the therapeutic potential of this molecule, the toxicity of systemic IL-12 treatment observed during clinical trials has limited its use (18,31,32,33,40). This toxicity correlates with increased IFN-␥ levels, decreased glucose levels, and altered histological responses in the spleen and duodenum. This has motivated several recent investigations demonstrating that intranasal delivery of IL-12 is a less toxic route of inoculation compared to the commonly used systemic one (6,7,26).The gram-positive and nonpathogenic...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice

Cortes-Perez

Ah‐Leung

Bermúdez‐Humarán

et al. 2007

Clin Vaccine Immunol

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“…A asma alérgica é uma doença inflamatória pulmonar crônica que pode ser caracterizada por uma broncoconstrição intermitente, reversível ou não, devida a hipersecreção de muco e reatividade brônquica exacerbada a diferentes estímulos, inflamação eosinofílica e alta produção de IgE (26) . A reação inflamatória pulmonar alérgica parece ser essencialmente .…”

Section: Asma Alérgicaunclassified

“…Este protocolo permite sincronizar, 24 h após o segundo desafio com OVA i.n., vários parâmetros alérgicos como hiperreatividade brônquica, formação de muco, produção de anticorpos anafiláticos (IgG1 e IgE), inflamação pulmonar eosinofílica, citocinas tipo 2 e patologia pulmonar (26,83,87,88) . O protocolo profilático consiste em administrar as cepas de BCG ou rBCG pela via intranasal, trinta dias antes da indução da inflamação alérgica pulmonar.…”

Section: Protocolo Profiláticounclassified

Modulação da resposta alérgica por BCG recombinante em modelo murino de asma.

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IL‐12 and IL‐4 activate a CD39‐dependent intrinsic peripheral tolerance mechanism in CD8⁺ T cells

et al. 2016

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Immune responses to protein antigens involve CD4+ and CD8+ T cells, which follow distinct programs of differentiation. Naïve CD8 T cells rapidly develop cytotoxic T‐cell (CTL) activity after T‐cell receptor stimulation, and we have previously shown that this is accompanied by suppressive activity in the presence of specific cytokines, i.e. IL‐12 and IL‐4. Cytokine‐induced CD8+ regulatory T (Treg) cells are one of several Treg‐cell phenotypes and are Foxp3− IL‐10+ with contact‐dependent suppressive capacity. Here, we show they also express high level CD39, an ecto‐nucleotidase that degrades extracellular ATP, and this contributes to their suppressive activity. CD39 expression was found to be upregulated on CD8+ T cells during peripheral tolerance induction in vivo, accompanied by release of IL‐12 and IL‐10. CD39 was also upregulated during respiratory tolerance induction to inhaled allergen and on tumor‐infiltrating CD8+ T cells. Production of IL‐10 and expression of CD39 by CD8+ T cells was independently regulated, being respectively blocked by extracellular ATP and enhanced by an A2A adenosine receptor agonist. Our results suggest that any CTL can develop suppressive activity when exposed to specific cytokines in the absence of alarmins. Thus negative feedback controls CTL expansion under regulation from both nucleotide and cytokine environment within tissues.

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Hierarchical suppression of asthma-like responses by mucosal tolerance

Cited by 49 publications

References 21 publications

Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice

Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice

Modulação da resposta alérgica por BCG recombinante em modelo murino de asma.

IL‐12 and IL‐4 activate a CD39‐dependent intrinsic peripheral tolerance mechanism in CD8⁺ T cells

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Hierarchical suppression of asthma-like responses by mucosal tolerance

Cited by 49 publications

References 21 publications

Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice

Intranasal Coadministration of Live Lactococci Producing Interleukin-12 and a Major Cow's Milk Allergen Inhibits Allergic Reaction in Mice

Modulação da resposta alérgica por BCG recombinante em modelo murino de asma.

IL‐12 and IL‐4 activate a CD39‐dependent intrinsic peripheral tolerance mechanism in CD8+ T cells

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Product

Resources

About

IL‐12 and IL‐4 activate a CD39‐dependent intrinsic peripheral tolerance mechanism in CD8⁺ T cells