Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
Yuna Jo, Bo-Young Kim, So Min Lee, Ji‐Su Park, Woo Seok Kim, Ju A Shim, Jun Hong Park, Jong‐Eun Park, Yong‐Il Shin, Ji Hyeon Ryu, Changwan Hong
Abstract
Particulate matter (PM) is a harmful air pollutant associated with respiratory and cardiovascular diseases, but its effects on adaptive immunity are poorly understood. This study investigates the role of NRF2 in T cells in mediating immune and pulmonary responses to long-term PM exposure, highlighting its impact on inhalation toxicity. To establish a mouse model of lung injury induced by PM exposure, C57BL/6 mice were intranasally administered 20 μg/kg PM 10 or PM 2.5 daily for 16 weeks. Lung injury parameters were analyzed in bronchoalveolar lavage fluid (BALF), plasma, and lung tissue. Changes in the proportion of immune cells in the lymph nodes and spleen were analyzed. Mice exposed to PM for 16 weeks showed severe lung damage, such as inflammatory cell infiltration, thickened alveolar walls, and increased oxidative stress and apoptosis. PM exposure also increased collagen and fibronectin levels, indicating tissue remodeling. Immune cell analysis revealed reduced B cell expansion, increased IL-4-producing CD4 + T cells, and decreased IFN-γ- and TNF-α-producing CD4 + T cells, accompanied by higher T H 2 cytokines and plasma IgE and IgG1 levels. PM activated the NRF2 pathway, skewing immune responses toward T H 2 differentiation, which worsened lung inflammation. These findings highlight how PM exposure disrupts immune balance and exacerbates conditions like asthma and chronic obstructive pulmonary disease by promoting T H 2-driven inflammation through NRF2 activation. • Smaller PM intensifies lung inflammation and fibrosis, exerting more severe effects on pulmonary health. • PM exposure alters immune cell composition, reducing B cells while increasing T cells and CD4:CD8 ratio. • PM suppresses T H 1 responses and promotes T H 2-related cytokines, shifting overall immune response. • PM exposure elevates T H 2 cytokines, IgE, and IgG1 levels, indicating T H 2 polarization, especially with PM 2.5 . • PM upregulates NRF2 and its downstream genes, promoting T H 2 differentiation and pulmonary inflammation.