Acrylamide, an air pollutant, enhances allergen-induced eosinophilic lung inflammation via group 2 innate lymphoid cells.

Abstract

Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s. Intranasal acrylamide exposure at nanomolar levels significantly enhanced allergen-induced or recombinant mouse interleukin-33-induced lung inflammation in C57BL/6 mice or Rag1-/- mice, respectively. The cardinal features of lung inflammation included accumulated infiltration of ILC2s and eosinophils. Transcriptomic analysis revealed a gene expression pattern associated with proliferation-related pathways in acrylamide-treated ILC2s. Western blotting revealed significantly higher expression of Ras and phospho-Erk in acrylamide-treated ILC2s than the control, suggesting Ras-Erk signaling pathway involvement. Ex vivo and in vitro analysis showed that acrylamide treatment mainly increased Ki-67+ ILC2s and the cell number of ILC2s whereas PD98059, a highly selective Erk inhibitor, effectively counteracted the acrylamide effect. Intratracheal administration of acrylamide-treated ILC2s significantly enhanced eosinophil infiltration in Rag1-/- mice. This study suggests that airborne acrylamide may enhance the severity of allergen-induced airway eosinophilic inflammation, partly via altering ILC2 proliferative activity.

• Authors: Hsiang-Han Su, Chih-Mei Cheng, Yung-Ning Yang, Yu-Wei Chang, Chia-Yang Li, Shin-Ting Wu, Chia-Chi Lin, Hsin-En Wu, Jau-Ling Suen
• Journal: Mucosal immunology (Mucosal Immunol) Vol. 17 Issue 1 Pg. 13-24 (Feb 2024) ISSN: 1935-3456 [Electronic] United States
• PMID: 37805143 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Allergens
• Air Pollutants
• Acrylamides
• Homeodomain Proteins
• Interleukin-33
• Cytokines

Topics

• Mice
• Animals
• Immunity, Innate
• Allergens
• Air Pollutants
• Lymphocytes
• Mice, Inbred C57BL
• Pulmonary Eosinophilia
• Pneumonia
• Acrylamides
• Homeodomain Proteins (genetics)
• Lung
• Interleukin-33 (metabolism)
• Cytokines (metabolism)