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Article Dans Une Revue Journal of Allergy and Clinical Immunology Année : 2017

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

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Louis Fauconnier
  • Fonction : Auteur
Tiffany Marchiol
Nathalie Rouxel
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Aurélie Ledru
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Margaux Gallerand
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Lionel Apetoh
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Fabrice Trovero
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Dieudonnée Togbe
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Résumé

BACKGROUND: Protein kinase C (PKC) θ, a serine/threonine kinase, is involved in TH2 cell activation and proliferation. Type 2 innate lymphoid cells (ILC2s) resemble TH2 cells and produce the TH2 cytokines IL-5 and IL-13 but lack antigen-specific receptors. The mechanism by which PKC-θ drives innate immune cells to instruct TH2 responses in patients with allergic lung inflammation remains unknown. OBJECTIVES: We hypothesized that PKC-θ contributes to ILC2 activation and might be necessary for ILC2s to instruct the TH2 response. METHODS: PRKCQ gene expression was assessed in innate lymphoid cell subsets purified from human PBMCs and mouse lung ILC2s. ILC2 activation and eosinophil recruitment, TH2-related cytokine and chemokine production, lung histopathology, interferon regulatory factor 4 (IRF4) mRNA expression, and nuclear factor of activated T cells (NFAT1) protein expression were determined. Adoptive transfer of ILC2s from wild-type mice was performed in wild-type and PKC-θ-deficient (PKC-θ-/-) mice. RESULTS: Here we report that PKC-θ is expressed in both human and mouse ILC2s. Mice lacking PKC-θ had reduced ILC2 numbers, TH2 cell numbers and activation, airway hyperresponsiveness, and expression of the transcription factors IRF4 and NFAT1. Importantly, adoptive transfer of ILC2s restored eosinophil influx and IL-4, IL-5 and IL-13 production in lung tissue, as well as TH2 cell activation. The pharmacologic PKC-θ inhibitor (Compound 20) administered during allergen challenge reduced ILC2 numbers and activation, as well as airway inflammation and IRF4 and NFAT1 expression. CONCLUSIONS: Therefore our findings identify PKC-θ as a critical factor for ILC2 activation that contributes to TH2 cell differentiation, which is associated with IRF4 and NFAT1 expression in allergic lung inflammation.

Dates et versions

hal-01512634 , version 1 (24-04-2017)

Identifiants

Citer

Fahima Madouri, Pauline Chenuet, Chloé Beuraud, Louis Fauconnier, Tiffany Marchiol, et al.. Protein kinase C θ controls type 2 innate lymphoid cell and TH2 responses to house dust mite allergen.. Journal of Allergy and Clinical Immunology, 2017, 139 (5), pp.1650-1666. ⟨10.1016/j.jaci.2016.08.044⟩. ⟨hal-01512634⟩
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