NLRP6 negatively regulates type 2 immune responses in mice - Centre d’Etude des Pathologies Respiratoires (CEPR), UMR 1100 Accéder directement au contenu
Article Dans Une Revue Allergy Année : 2022

NLRP6 negatively regulates type 2 immune responses in mice

Pauline Chenuet
  • Fonction : Auteur
Louis Fauconnier
  • Fonction : Auteur
Manon Mellier
  • Fonction : Auteur
Tiffany Marchiol
  • Fonction : Auteur
Nathalie Rouxel
  • Fonction : Auteur
Aurélie Ledru
  • Fonction : Auteur

Résumé

Background: Inflammasomes are large protein complexes that assemble in the cytosol in response to danger such as tissue damage or infection. Following activation, inflammasomes trigger cell death and the release of biologically active forms of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. NOD-like receptor family pyrin domain containing 6 (NLRP6) inflammasome is required for IL-18 secretion by intestinal epithelial cells, macrophages, and T cells, contributing to homeostasis and self-defense against pathogenic microbes. However, the involvement of NLRP6 in type 2 lung inflammation remains elusive. Methods: Wild-type (WT) and Nlrp6−/− mice were used. Birch pollen extract (BPE)-induced allergic lung inflammation, eosinophil recruitment, Th2-related cytokine and chemokine production, airway hyperresponsiveness, and lung histopathology, Th2 cell differentiation, GATA3, and Th2 cytokines expression, were determined. Nippostrongylus brasiliensis (Nb) infection, worm count in intestine, type 2 innate lymphoid cell (ILC2), and Th2 cells in lungs were evaluated. Results: We demonstrate in Nlrp6−/− mice that a mixed Th2/Th17 immune responses prevailed following birch pollen challenge with increased eosinophils, ILC2, Th2, and Th17 cell induction and reduced IL-18 production. Nippostrongylus brasiliensis infected Nlrp6−/− mice featured enhanced early expulsion of the parasite due to enhanced type 2 immune responses compared to WT hosts. In vitro, NLRP6 repressed Th2 polarization, as shown by increased Th2 cytokines and higher expression of the transcription factor GATA3 in the absence of NLRP6. Exogenous IL-18 administration partially reduced the enhanced airways inflammation in Nlrp6−/− mice. Conclusions: In summary, our data identify NLRP6 as a negative regulator of type 2 immune responses.
Fichier principal
Vignette du fichier
Allergy_2022_NLRP6.pdf (10.82 Mo) Télécharger le fichier
Origine : Publication financée par une institution

Dates et versions

hal-03770030 , version 1 (06-09-2022)

Licence

Paternité - Pas d'utilisation commerciale - Pas de modification

Identifiants

Citer

Pauline Chenuet, Quentin Marquant, Louis Fauconnier, Ali Youness, Manon Mellier, et al.. NLRP6 negatively regulates type 2 immune responses in mice. Allergy, In press, ⟨10.1111/all.15388⟩. ⟨hal-03770030⟩
62 Consultations
456 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More