Effects of Air Pollution on Lung Innate Lymphoid Cells: Review of In Vitro and In Vivo Experimental Studies

Abstract

Outdoor air pollution is associated with respiratory infections and allergies, yet the role of innate lymphoid cells (ILCs) in pathogen containment and airway hyperresponsiveness relevant to effects of air pollutants on ILCs is poorly understood. We conducted a systematic review to evaluate the available evidence on the effect of outdoor air pollutants on the lung type 1 (ILC1) and type 2 ILCs (ILC2) subsets. We searched five electronic databases (up to Dec 2018) for studies on the effect of carbon monoxide (CO), sulfur dioxide (SO2), nitrogen dioxide (NO2), diesel exhaust particles (DEP), ozone (O3), and particulate matter (PM) on respiratory ILCs. Of 2209 identified citations, 22 full-text papers were assessed for eligibility, and 12 articles describing experimental studies performed in murine strains (9) and on human blood cells (3) were finally selected. Overall, these studies showed that exposure to PM, DEP, and high doses of O3 resulted in a reduction of interferon gamma (IFN-γ) production and cytotoxicity of ILC1. These pollutants and carbon nanotubes stimulate lung ILC2s, produce high levels of interleukin (IL)-5 and IL-13, and induce airway hyperresponsiveness. These findings highlight potential mechanisms by which human ILCs react to air pollution that increase the susceptibility to infections and allergies.

The effect of air pollutants on airway innate immune cells in patients with asthma

“…Studies in mice have revealed that DEP, O 3 , and multi-wall carbon nanotubes activate ILC2s to produce IL-5 and IL-13 in response to IL-33 produced by airway epithelial cells. 4 In the current study, only PM 10 levels positively correlated with the proportion of ILC2s. However, previous studies showed that O 3 , a potent oxidizing agent, induced type 2 cytokine secretion from ILC2s.…”

The Effect of Air Pollution on the Transcriptomics of the Immune Response to Respiratory Infection

“…In terms of immune effects, decreased levels of IFN-γ (important for macrophage activation) were observed in the peripheral blood of mice exposed to traffic pollution in China [12], and in the peripheral blood of humans exposed to diesel exhaust [33]. Further research has also observed dysregulation of the epithelial cell junction, respiratory microbiome and cytokine response as additional factors increasing pathogenic virulence in the setting of PM exposure [34].…”

Senescence in Pulmonary Fibrosis: Between Aging and Exposure

“…At the levels of mucus producing cells (goblet cells), PM results in MUC5B hypersecretion (103). Furthermore, PM engages and functionally impacts innate like cells type 1 (ILC1), thereby blunting their interferon gamma (IFN-γ) production and cytotoxic function; induces antigen-presenting cell-mediated inflammatory responses, while impairing their migration; enhanced neutrophil and eosinophil responses; and shifts lymphocyte differentiation toward an effector phenotype (Th1-like) (108)(109)(110)(111). Lastly, the effects on endothelial function (disruption of tight junctions) have significant repercussion on the susceptibility to cardiovascular disease and infarction (112)(113)(114)(115).…”