Protein kinase Cθ controls type 2 innate lymphoid cell and TH2 responses to house dust mite allergen

Madouri, Fahima; Chenuet, Pauline; Beuraud, Chloé; Fauconnier, Louis; Marchiol, Tiffany; Rouxel, Nathalie; Ledru, Aurélie; Gallerand, Margaux; Lombardi, Vincent; Mascarell, Laurent; Marquant, Quentin; Apétoh, Lionel; Erard, François; Bert, Marc Le; Trovero, Fabrice; Quesniaux, Valérie; Ryffel, Bernhard; Togbé, Dieudonnée

doi:10.1016/j.jaci.2016.08.044

Cited by 23 publications

(23 citation statements)

References 38 publications

(38 reference statements)

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“…The latter population is known to precede Th2 activation which is the cardinal feature of allergic asthma, culminating in airway hyperresponsiveness and Th2 cytokines and chemokines. In this setting, we investigated IL-33, which is known to be involved in ILC2 activation 35 but we did not find any difference upon ECN treatment, which was also the case in another reduced allergic asthma condition 57 .…”

Section: Discussionmentioning

confidence: 89%

The probiotic strain Escherichia coli Nissle 1917 prevents papain-induced respiratory barrier injury and severe allergic inflammation in mice

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Maillet

Mackowiak

et al. 2018

Sci Rep

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Allergic asthma is characterized by a strong Th2 and Th17 response with inflammatory cell recruitment, airways hyperreactivity and structural changes in the lung. The protease allergen papain disrupts the airway epithelium triggering a rapid eosinophilic inflammation by innate lymphoid cell type 2 (ILC2) activation, leading to a Th2 immune response. Here we asked whether the daily oral administrations of the probiotic Escherichia coli strain Nissle 1917 (ECN) might affect the outcome of the papain protease induced allergic lung inflammation in BL6 mice. We find that ECN gavage significantly prevented the severe allergic response induced by repeated papain challenges and reduced lung inflammatory cell recruitment, Th2 and Th17 response and respiratory epithelial barrier disruption with emphysema and airway hyperreactivity. In conclusion, ECN administration attenuated severe protease induced allergic inflammation, which may be beneficial to prevent allergic asthma.

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Section: Discussionmentioning

confidence: 89%

The probiotic strain Escherichia coli Nissle 1917 prevents papain-induced respiratory barrier injury and severe allergic inflammation in mice

Sécher

Maillet

Mackowiak

et al. 2018

Sci Rep

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“…Therefore, PKC‐θ signalling is crucial for the recruitment of pathogenic CD8 + T cells and development ECM. However, it was recently shown that ILC2 also express PKC‐θ (Figure ) . Thus, the absence of PKC‐θ might have impacted not only pathogenic T‐cell response but also protective ILC2 in this setting which deserves further investigations.…”

Section: Ilc2 Th2 Cells and Pkc‐θ Activationmentioning

confidence: 90%

Unravelling the roles of innate lymphoid cells in cerebral malaria pathogenesis

Palomo

Quesniaux

Togbé

et al. 2018

Parasite Immunology

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Cerebral malaria (CM) is one complication of Plasmodium parasite infection that can lead to strong inflammatory immune responses in the central nervous system (CNS), accompanied by lung inflammation and anaemia. Here, we focus on the role of the innate immune response in experimental cerebral malaria (ECM) caused by blood-stage murine Plasmodium berghei ANKA infection. While T cells are important for ECM pathogenesis, the role of innate lymphoid cells (ILCs) is only emerging. The role of ILCs and non-lymphoid cells, such as neutrophils and platelets, contributing to the host immune response and leading to ECM and human cerebral malaria (HCM) is reviewed.

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“…Thus, Nrf2 activators are expected to serve as useful therapeutic agents for asthma, with less adverse effects than dexamethasone. Apart from Nrf2, other possible intervention targets for ILC2s include a PKC inhibitor C-20, which reduces the ILC2 cell numbers and activation and decreases airway inflammation (32). C-20 suppresses IRF4 and NFAT1 expression, thus attenuating ILC2 homeostasis and function, and miR-19, which targets both A20 (a negative regulator of NF-kB) and SOCS1 (an inhibitor of the JAK-STAT pathway), thereby regulates ILC2s' effector function (33).…”

Section: Discussionmentioning

confidence: 99%

Nrf2 Suppresses Allergic Lung Inflammation by Attenuating the Type 2 Innate Lymphoid Cell Response

Nagashima

Kosai

Masuo

et al. 2019

The Journal of Immunology

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The Keap1-Nrf2 system plays a pivotal role in the oxidative stress response by inducing a number of cytoprotective genes. Under stress, damaged epithelial cells release cytokines that activate type 2 innate lymphoid cells (ILC2s), which mediate the allergic immune response. In this article, we investigated the role of the Keap1-Nrf2 pathway in ILC2 homeostasis and allergic inflammation using Nrf2 knockout mice. ILC2s from Nrf2-deficient mice showed a transient, upregulated IL-33 response and underwent hyperproliferation in response to a combined stimulation of IL-33 with IL-2, IL-7, or TSLP. This enhanced proliferation was correlated with an increased activation of downstream signals, including JAK1, Akt, and Erk1/2. In contrast, activating Nrf2 with a chemical inducer (CDDO-Im) decreased the viability of the wild-type but not of the Nrf2-deficient ILC2s. This effect on viability resembled that exerted by the corticosteroid dexamethasone; however, unlike the latter, the Nrf2-dependent cell death was mediated by neither caspase 3-dependent apoptosis nor necroptosis. Using a mouse intratracheal IL-33 administration allergy model, we found that the activation of Nrf2 by CDDO-Im in vivo decreased the number of pulmonary ILC2s and eosinophils. These findings indicated that Nrf2 is an important regulator of the allergic response by determining the survival and death of ILC2s, and these findings suggest that Nrf2 activation is a potential therapeutic strategy for steroid-resistant allergy alleviation.

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Protein kinase Cθ controls type 2 innate lymphoid cell and TH2 responses to house dust mite allergen

Abstract: Therefore our findings identify PKC-θ as a critical factor for ILC2 activation that contributes to T2 cell differentiation, which is associated with IRF4 and NFAT1 expression in allergic lung inflammation.

Cited by 23 publications

References 38 publications

The probiotic strain Escherichia coli Nissle 1917 prevents papain-induced respiratory barrier injury and severe allergic inflammation in mice

The probiotic strain Escherichia coli Nissle 1917 prevents papain-induced respiratory barrier injury and severe allergic inflammation in mice

Unravelling the roles of innate lymphoid cells in cerebral malaria pathogenesis

Nrf2 Suppresses Allergic Lung Inflammation by Attenuating the Type 2 Innate Lymphoid Cell Response

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