Air Pollution Drives Allergic-Type Immune Imbalance & Lung Damage

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Air pollution may promote asthma and worsen lung diseases by altering immune regulation and increasing oxidative stress, according to recent research on mice.

Chronic inhalation of particulate matter (PM) drove oxidative‑stress-mediated shifts toward allergic-type immune imbalance, aggravated fibrosis, and suppressed protective T helper 1 (TH1) signals in a mouse model, according to a study published in Redox Biology.

“Particulate matter (PM) is a harmful air pollutant associated with respiratory and cardiovascular diseases, but its effects on adaptive immunity are poorly understood,” wrote corresponding study author Changwan Hong, PhD, of Pusan National University, and colleagues.

“Our study reveals how chronic exposure to particulate matter (PM10 and PM2.5) triggers harmful allergic‑like (TH2) immune responses in the lungs by activating oxidative stress and the NRF2 [nuclear factor erythroid 2-related factor 2] pathway,” explained Dr. Hong in a news release.

Pollution Tips the Immune Scales 

To establish a mouse model of PM-induced lung injury, the authors intranasally administered PM10 or PM2.5 to mice daily for 16 weeks, then analyzed lung injury parameters in bronchoalveolar lavage fluid, plasma, and lung tissue. Changes in the proportion of immune cells in the lymph nodes and spleen were also analyzed.

According to findings, daily intranasal PM dosing thickened alveolar walls, recruited macrophages and neutrophils, and increased collagen deposition—changes that were markedly worse with exposure to PM2.5, which is known to penetrate the lungs more deeply. The authors also observed a marked shift in immune response; immune profiling revealed a sharp increase in interleukin (IL)-4-, IL-5-, and IL-13-producing cluster of differentiation 4 (CD4⁺) cells, accompanied by higher plasma immunoglobulin (Ig)E and IgG1 levels. At the same time, interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α) production decreased.

“Following PM exposure, pro-inflammatory markers … trigger inflammatory responses in lung tissue, regulate the immune cell functions, and exacerbate lung damage and inflammation,” the authors stated.

NRF2: Protector Turned Provocateur

According to the authors, PM amplified reactive‑oxygen species and 4-hydroxynonenal, up‑regulating nuclear respiratory factor 2 (NRF2) and its antioxidant targets (glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1, and heme oxygenase-1). In this setting, sustained NRF2 signaling favored TH2 polarization and impaired autophagy. Experiments in Nrf2‑deficient and transgenic mice confirmed the transcription factor’s central role: loss of Nrf2 restored IFN‑γ, limited fibrosis, and preserved lung architecture, whereas overexpression intensified TH2 skewing.

“This mechanistic link explains why air pollution can worsen asthma and other allergic diseases, identifying NRF2 as a key driver of this shift,” Dr. Hong noted.

Clinical Implications for Patient Care

“This study provides valuable insights into the complex interplay between environmental pollutants, immune responses, and respiratory health,” the authors stated. “Our findings reveal novel mechanisms by which particulate matter exposure influences disease development, particularly through its effects on immune cell function and differentiation.”

Dr. Hong added, “Our findings suggest that targeting oxidative stress or modulating NRF2 activity could be a new strategy to treat or prevent pollution‑induced allergic inflammation, such as asthma.”