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Ezh2 controls development of natural killer T cells, which cause spontaneous asthma-like pathology.
- Source :
-
The Journal of allergy and clinical immunology [J Allergy Clin Immunol] 2019 Aug; Vol. 144 (2), pp. 549-560.e10. Date of Electronic Publication: 2019 Mar 07. - Publication Year :
- 2019
-
Abstract
- Background: Natural killer T (NKT) cells express a T-cell receptor that recognizes endogenous and environmental glycolipid antigens. Several subsets of NKT cells have been identified, including IFN-γ-producing NKT1 cells, IL-4-producing NKT2 cells, and IL-17-producing NKT17 cells. However, little is known about the factors that regulate their differentiation and respective functions within the immune system.<br />Objective: We sought to determine whether the polycomb repressive complex 2 protein enhancer of zeste homolog 2 (Ezh2) restrains pathogenicity of NKT cells in the context of asthma-like lung disease.<br />Methods: Numbers of invariant natural killer T (iNKT) 1, iNKT2, and iNKT17 cells and tissue distribution, cytokine production, lymphoid tissue localization, and transcriptional profiles of iNKT cells from wild-type and Ezh2 knockout (KO) iNKT mice were determined. The contribution of NKT cells to development of spontaneous and house dust mite-induced airways pathology, including airways hyperreactivity (AHR) to methacholine, was also assessed in wild-type, Ezh2 KO, and Ezh2 KO mice lacking NKT cells.<br />Results: Ezh2 restrains development of pathogenic NKT cells, which induce spontaneous asthma-like disease in mice. Deletion of Ezh2 increased production of IL-4 and IL-13 and induced spontaneous AHR, lung inflammation, mucus production, and IgE. Increased IL-4 and IL-13 levels, AHR, lung inflammation, and IgE levels were all dependent on iNKT cells. In house dust mite-exposed animals Ezh2 KO resulted in enhanced AHR that was also dependent on iNKT cells.<br />Conclusion: Ezh2 is a central regulator of iNKT pathogenicity and suppresses the ability of iNKT cells to induce asthma-like pathology.<br /> (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Asthma genetics
Asthma pathology
Basic Helix-Loop-Helix Transcription Factors genetics
Basic Helix-Loop-Helix Transcription Factors immunology
Enhancer of Zeste Homolog 2 Protein genetics
Immunoglobulin E genetics
Immunoglobulin E immunology
Inflammation genetics
Inflammation immunology
Inflammation pathology
Interleukin-13 genetics
Interleukin-13 immunology
Interleukin-4 genetics
Interleukin-4 immunology
Lung pathology
Mice
Mice, Knockout
Natural Killer T-Cells pathology
Receptors, Aryl Hydrocarbon genetics
Receptors, Aryl Hydrocarbon immunology
Asthma immunology
Enhancer of Zeste Homolog 2 Protein immunology
Lung immunology
Natural Killer T-Cells immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1097-6825
- Volume :
- 144
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The Journal of allergy and clinical immunology
- Publication Type :
- Academic Journal
- Accession number :
- 30851295
- Full Text :
- https://doi.org/10.1016/j.jaci.2019.02.024