NLRP6 negatively regulates type 2 immune responses in mice.

Autor: Chenuet P; Artimmune SAS, Orléans, France., Marquant Q; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France., Fauconnier L; Artimmune SAS, Orléans, France., Youness A; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France., Mellier M; Artimmune SAS, Orléans, France., Marchiol T; Artimmune SAS, Orléans, France., Rouxel N; Artimmune SAS, Orléans, France., Messaoud-Nacer Y; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France., Maillet I; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France., Ledru A; Artimmune SAS, Orléans, France., Quesniaux VFJ; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France., Ryffel B; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France., Horsnell W; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France.; Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town 7925, South Africa & South African Medical Research Council, Cape Town, South Africa.; Institute of Microbiology and Infection, University of Birmingham, Birmingham, UK., Végran F; INSERM, U1231, Dijon, France., Apetoh L; INSERM, U1100, Tours, France., Togbe D; Laboratory of Experimental and Molecular Immunology and Neurogenetics (INEM), UMR 7355 CNRS-University of Orleans, Orleans-Cedex 2, France.
Jazyk: angličtina
Zdroj: Allergy [Allergy] 2022 Nov; Vol. 77 (11), pp. 3320-3336. Date of Electronic Publication: 2022 Jun 10.
DOI: 10.1111/all.15388
Abstrakt: 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.
(© 2022 The Authors. Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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