Regulation of type 2 innate lymphoid cell–dependent airway hyperreactivity by butyrate - 06/12/18
Abstract |
Background |
Allergic asthma is characterized by airway hyperreactivity (AHR) and inflammation driven by aberrant TH2 responses. Type 2 innate lymphoid cells (ILC2s) are a critical source of the TH2 cytokines IL-5 and IL-13, which promote acute asthma exacerbation. Short-chain fatty acids (SCFAs) have been shown to attenuate T cell–mediated allergic airway inflammation. However, their role in regulation of ILC2-driven AHR and lung inflammation remains unknown.
Objective |
We investigated the immunomodulatory role of SCFAs in regulation of ILC2-induced AHR and airway inflammation and delineated the mechanism involved.
Methods |
We assessed the role of SCFAs in regulating survival, proliferation, and cytokine production in lung sorted ILC2s. The SCFA butyrate was administered through drinking water or intranasally in BALB/c mice to evaluate its role in the ILC2-driven inflammatory response in IL-33 and Alternaria alternata models of allergic inflammation. We further confirmed our findings in human ILC2s.
Results |
We show that butyrate, but not acetate or propionate, inhibited IL-13 and IL-5 production by murine ILC2s. Systemic and local administration of butyrate significantly ameliorated ILC2-driven AHR and airway inflammation. We further demonstrate that butyrate inhibited ILC2 proliferation and GATA3 expression but did not induce cell apoptosis, likely through histone deacetylase (HDAC) inhibition, because trichostatin A, a pan-HDAC inhibitor, exerted similar effects on ILC2s. Importantly, cotreatment with trichostatin A and butyrate did not result in an additive effect. Finally, we show that butyrate reduces cytokine production in human ILC2s.
Conclusion |
Our findings identify butyrate as a critical regulator of ILC2 proliferation and function through its HDAC inhibitory activity and can serve as a potential therapeutic target for asthma.
Le texte complet de cet article est disponible en PDF.Graphical abstract |
Key words : Short-chain fatty acids, butyrate, type 2 innate lymphoid cells, allergic asthma, eosinophilic airway inflammation
Abbreviations used : AHR, BALF, ERK, Foxp3, FVD, GPR, HDAC, ICOS, ILC, ILC2, NF-κB, PI, PMA, Rag2, SCFA, TSA, TCR, Treg
Plan
Supported in part by the Ministry of Science and Technology (105-2628-B-001-009-MY3 and 105-2320-B-001-001 to Y.-J.C.) and by the Academia Sinica Career Development Award (104-CDA-L05 to Y.-J.C.) in Taiwan. |
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Disclosure of potential conflict of interest: Y.-J. Chang reports grant funding from the Ministry of Science & Technology (MOST) and a career development award from Academia Sinica. The rest of the authors declare that they have no relevant conflicts of interest. |
Vol 142 - N° 6
P. 1867 - décembre 2018 Retour au numéroBienvenue sur EM-consulte, la référence des professionnels de santé.
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