Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice

Introduction: Particulate matter (PM) is a harmful air pollutant associated with respiratory and cardiovascular diseases, but its effects on adaptive immunity are poorly understood. Objectives: This study investigates the role of NRF2 in T cells in mediating immune and pulmonary responses to long-te...

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Main Authors: Yuna Jo, Bo-Young Kim, So Min Lee, Jisu Park, Wooseok Kim, Ju A Shim, Jun Hong Park, Jong-Eun Park, Yong-Il Shin, Ji Hyeon Ryu, Changwan Hong
Format: Article
Language:English
Published: Elsevier 2025-05-01
Series:Redox Biology
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Online Access:http://www.sciencedirect.com/science/article/pii/S2213231725001454
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author Yuna Jo
Bo-Young Kim
So Min Lee
Jisu Park
Wooseok Kim
Ju A Shim
Jun Hong Park
Jong-Eun Park
Yong-Il Shin
Ji Hyeon Ryu
Changwan Hong
author_facet Yuna Jo
Bo-Young Kim
So Min Lee
Jisu Park
Wooseok Kim
Ju A Shim
Jun Hong Park
Jong-Eun Park
Yong-Il Shin
Ji Hyeon Ryu
Changwan Hong
author_sort Yuna Jo
collection DOAJ
description Introduction: Particulate matter (PM) is a harmful air pollutant associated with respiratory and cardiovascular diseases, but its effects on adaptive immunity are poorly understood. Objectives: 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. Methods: To establish a mouse model of lung injury induced by PM exposure, C57BL/6 mice were intranasally administered 20 μg/kg PM10 or PM2.5 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. Results: 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 TH2 cytokines and plasma IgE and IgG1 levels. PM activated the NRF2 pathway, skewing immune responses toward TH2 differentiation, which worsened lung inflammation. Conclusions: These findings highlight how PM exposure disrupts immune balance and exacerbates conditions like asthma and chronic obstructive pulmonary disease by promoting TH2-driven inflammation through NRF2 activation.
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spelling doaj-art-6dda6781148844beb0e3fb2192f60a2e2025-08-20T03:14:45ZengElsevierRedox Biology2213-23172025-05-018210363210.1016/j.redox.2025.103632Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in miceYuna Jo0Bo-Young Kim1So Min Lee2Jisu Park3Wooseok Kim4Ju A Shim5Jun Hong Park6Jong-Eun Park7Yong-Il Shin8Ji Hyeon Ryu9Changwan Hong10Department of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of KoreaDepartment of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, Republic of Korea; PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaDepartment of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, Republic of KoreaDepartment of Physiology, College of Veterinary Medicine, Jeonbuk National University, Iksan, Republic of KoreaGraduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Department of Rehabilitation Medicine, Pusan National University School of Medicine, Yangsan, Republic of KoreaResearch Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Corresponding author. Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea.Department of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of Korea; Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Republic of Korea; Department of Convergence Medical Science, Pusan National University School of Medicine, Yangsan, Republic of Korea; PNU GRAND Convergence Medical Science Education Research Center, Pusan National University School of Medicine, Yangsan, Republic of Korea; Corresponding author. Department of Anatomy, Pusan National University School of Medicine, Yangsan, Republic of KoreaIntroduction: Particulate matter (PM) is a harmful air pollutant associated with respiratory and cardiovascular diseases, but its effects on adaptive immunity are poorly understood. Objectives: 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. Methods: To establish a mouse model of lung injury induced by PM exposure, C57BL/6 mice were intranasally administered 20 μg/kg PM10 or PM2.5 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. Results: 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 TH2 cytokines and plasma IgE and IgG1 levels. PM activated the NRF2 pathway, skewing immune responses toward TH2 differentiation, which worsened lung inflammation. Conclusions: These findings highlight how PM exposure disrupts immune balance and exacerbates conditions like asthma and chronic obstructive pulmonary disease by promoting TH2-driven inflammation through NRF2 activation.http://www.sciencedirect.com/science/article/pii/S2213231725001454NRF2Oxidative stressParticulate matterTh2 immunity
spellingShingle Yuna Jo
Bo-Young Kim
So Min Lee
Jisu Park
Wooseok Kim
Ju A Shim
Jun Hong Park
Jong-Eun Park
Yong-Il Shin
Ji Hyeon Ryu
Changwan Hong
Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
Redox Biology
NRF2
Oxidative stress
Particulate matter
Th2 immunity
title Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
title_full Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
title_fullStr Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
title_full_unstemmed Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
title_short Particulate matter exposure induces pulmonary TH2 responses and oxidative stress-mediated NRF2 activation in mice
title_sort particulate matter exposure induces pulmonary th2 responses and oxidative stress mediated nrf2 activation in mice
topic NRF2
Oxidative stress
Particulate matter
Th2 immunity
url http://www.sciencedirect.com/science/article/pii/S2213231725001454
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