Protein kinase C? controls type 2 innate lymphoid cell and TH2 responses to house dust mite allergen - 27/09/17
Abstract |
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.
Le texte complet de cet article est disponible en PDF.Key words : House dust mite, allergic asthma, eosinophils, protein kinase Cθ, innate lymphoid cells, nuclear factor of activated T cells, interferon regulatory factor 4
Abbreviations used : BAL, BALF, BMDC, C20, DC, EPO, FACS, FoxP3, HDM, ILC, ILC1, ILC2, ILC3, IRF4, NFAT1, NK, OVA, PAS, PE, PKC, TCR, Treg, WT
Plan
Supported by ArtImmune, University of Orleans, la Région Centre (HabitAsthme no. 2012-00073535 and Inflammation et Infection no. 2013-00085470)m and Conseil Général 45 to F. Madouri, PhD fellowship. C.B. was supported by a CIFRE PhD fellowship from ANRT (Association Nationale de la Recherche et de la Technologie). |
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Disclosure of potential conflict of interest: C. Beuraud has received a grant from Association Nationale Rechereche Technologie and is employed by Stallergenes-Greer. L. Fauconnier, T. Marchiol, N. Rouxel, A. Ledru, F. Trovero, and D. Togbe are employed by ArtImmune SAS. V. Lombardi and L. Mascarell are employed by Stallergenes-Greer. V. F. J. Quesniaux has received grants from Region Centre (HabitAsthme mo. 2012-00073535 and Inflammation et Infection mo. 2013-00085470). The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 139 - N° 5
P. 1650-1666 - mai 2017 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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