Non-allergic eosinophilic inflammation and airway hyperresponsiveness induced by diesel engine exhaust through activating ILCs

Ecotoxicol Environ Saf. 2024 Jun 15:278:116403. doi: 10.1016/j.ecoenv.2024.116403. Epub 2024 May 5.

Abstract

Rationale: Diesel engine exhaust (DEE) is associated with the development and exacerbation of asthma. Studies have shown that DEE can aggravate allergen-induced eosinophilic inflammation in lung. However, it remains not clear that whether DEE alone could initiate non-allergic eosinophilic inflammation and airway hyperresponsiveness (AHR) through innate lymphoid cells (ILCs) pathway.

Objective: This study aims to investigate the airway inflammation and hyperresponsiveness and its relationship with ILC after DEE exposure.

Method: Non-sensitized BALB/c mice were exposed in the chamber of diesel exhaust or filtered air for 2, 4, and 6 weeks (4 h/day, 6 days/week). Anti-CD4 mAb or anti-Thy1.2 mAb was administered by intraperitoneal injection to inhibit CD4+T or ILCs respectively. AHR、airway inflammation and ILCs were assessed.

Result: DEE exposure induced significantly elevated level of neutrophils, eosinophils, collagen content at 4, 6 weeks. Importantly, the airway AHR was only significant in the 4weeks-DEE exposure group. No difference of the functional proportions of Th2 cells was found between exposure group and control group. The proportions of IL-5+ILC2, IL-17+ILC significantly increased in 2, 4weeks-DEE exposure group. After depletion of CD4+T cells, both the proportion of IL-5+ILC2 and IL-17A ILCs was higher in the 4weeks-DEE exposure group which induced AHR, neutrophilic and eosinophilic inflammation accompanied by the IL-5, IL-17A levels.

Conclusion: Diesel engine exhaust alone can imitate asthmatic characteristics in mice model. Lung-resident ILCs are one of the major effectors cells responsible for a mixed Th2/Th17 response and AHR.

Keywords: airway hyperresponsiveness; airway inflammation; diesel engine exhaust; innate lymphoid cells.

MeSH terms

  • Air Pollutants* / toxicity
  • Animals
  • Bronchoalveolar Lavage Fluid / cytology
  • Bronchoalveolar Lavage Fluid / immunology
  • Eosinophils / drug effects
  • Eosinophils / immunology
  • Female
  • Inflammation / chemically induced
  • Lymphocytes* / drug effects
  • Lymphocytes* / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C*
  • Respiratory Hypersensitivity / chemically induced
  • Respiratory Hypersensitivity / immunology
  • Vehicle Emissions* / toxicity

Substances

  • Vehicle Emissions
  • Air Pollutants