Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD

Group 2 innate lymphoid cells (ILC2) strongly modulate COPD pathogenesis. However, the significance of microbiota in ILC2s remains unelucidated. Herein, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) in regulating ILC2-associated airway inflammation and explores its ass...

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Main Authors: Min Jiang, Jing Wang, Zheng Li, Dan Xu, Jing Jing, Fengsen Li, Jianbing Ding, Qifeng Li
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2024/6263447
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author Min Jiang
Jing Wang
Zheng Li
Dan Xu
Jing Jing
Fengsen Li
Jianbing Ding
Qifeng Li
author_facet Min Jiang
Jing Wang
Zheng Li
Dan Xu
Jing Jing
Fengsen Li
Jianbing Ding
Qifeng Li
author_sort Min Jiang
collection DOAJ
description Group 2 innate lymphoid cells (ILC2) strongly modulate COPD pathogenesis. However, the significance of microbiota in ILC2s remains unelucidated. Herein, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) in regulating ILC2-associated airway inflammation and explores its associated mechanism in COPD. In particular, we assessed the SCFA-mediated regulation of survival, proliferation, and cytokine production in lung sorted ILC2s. To elucidate butyrate action in ILC2-driven inflammatory response in COPD models, we administered butyrate to BALB/c mice via drinking water. We revealed that SCFAs, especially butyrate, derived from dietary fiber fermentation by gut microbiota inhibited pulmonary ILC2 functions and suppressed both IL-13 and IL-5 synthesis by murine ILC2s. Using in vivo and in vitro experimentation, we validated that butyrate significantly ameliorated ILC2-induced inflammation. We further demonstrated that butyrate suppressed ILC2 proliferation and GATA3 expression. Additionally, butyrate potentially utilized histone deacetylase (HDAC) inhibition to enhance NFIL3 promoter acetylation, thereby augmenting its expression, which eventually inhibited cytokine production in ILC2s. Taken together, the aforementioned evidences demonstrated a previously unrecognized role of microbial-derived SCFAs on pulmonary ILC2s in COPD. Moreover, our evidences suggest that metabolomics and gut microbiota modulation may prevent lung inflammation of COPD.
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spelling doaj-art-eb527a8bf0cf4077a7230cef3672799b2025-08-20T03:21:16ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/6263447Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPDMin Jiang0Jing Wang1Zheng Li2Dan Xu3Jing Jing4Fengsen Li5Jianbing Ding6Qifeng Li7Xinjiang Key Laboratory of Respiratory Disease ResearchXinjiang Key Laboratory of Respiratory Disease ResearchXinjiang Key Laboratory of Respiratory Disease ResearchXinjiang Key Laboratory of Respiratory Disease ResearchXinjiang Key Laboratory of Respiratory Disease ResearchXinjiang Key Laboratory of Respiratory Disease ResearchDepartment of ImmunologyXinjiang Institute of PediatricsGroup 2 innate lymphoid cells (ILC2) strongly modulate COPD pathogenesis. However, the significance of microbiota in ILC2s remains unelucidated. Herein, we investigated the immunomodulatory role of short-chain fatty acids (SCFAs) in regulating ILC2-associated airway inflammation and explores its associated mechanism in COPD. In particular, we assessed the SCFA-mediated regulation of survival, proliferation, and cytokine production in lung sorted ILC2s. To elucidate butyrate action in ILC2-driven inflammatory response in COPD models, we administered butyrate to BALB/c mice via drinking water. We revealed that SCFAs, especially butyrate, derived from dietary fiber fermentation by gut microbiota inhibited pulmonary ILC2 functions and suppressed both IL-13 and IL-5 synthesis by murine ILC2s. Using in vivo and in vitro experimentation, we validated that butyrate significantly ameliorated ILC2-induced inflammation. We further demonstrated that butyrate suppressed ILC2 proliferation and GATA3 expression. Additionally, butyrate potentially utilized histone deacetylase (HDAC) inhibition to enhance NFIL3 promoter acetylation, thereby augmenting its expression, which eventually inhibited cytokine production in ILC2s. Taken together, the aforementioned evidences demonstrated a previously unrecognized role of microbial-derived SCFAs on pulmonary ILC2s in COPD. Moreover, our evidences suggest that metabolomics and gut microbiota modulation may prevent lung inflammation of COPD.http://dx.doi.org/10.1155/2024/6263447
spellingShingle Min Jiang
Jing Wang
Zheng Li
Dan Xu
Jing Jing
Fengsen Li
Jianbing Ding
Qifeng Li
Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD
Mediators of Inflammation
title Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD
title_full Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD
title_fullStr Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD
title_full_unstemmed Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD
title_short Dietary Fiber-Derived Microbial Butyrate Suppresses ILC2-Dependent Airway Inflammation in COPD
title_sort dietary fiber derived microbial butyrate suppresses ilc2 dependent airway inflammation in copd
url http://dx.doi.org/10.1155/2024/6263447
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