E-submission
Search
- Page Path
- HOME > Search
Original Articles
- Bronchial lesions in a high serum IgA mouse model: pulmonary venular IgA deposition and spatially distinct lymphoid cell aggregation
- Areum Kim, Minhyeok Lee, Yohan Park, Wan Jin Hwang, Hyeseung Lee, Joo Heon Kim, Jin Man Kim, Yong Min Kim, Jin Sun Park, Junguee Lee
- Received March 10, 2026 Accepted June 1, 2026 Published online July 16, 2026
- DOI: https://doi.org/10.4132/jptm.2026.06.01 [Epub ahead of print]
- 143 View
- 9 Download
-
Abstract
PDF - Background
Immunoglobulin A (IgA) nephropathy is a systemic immune complex–mediated disease primarily affecting the kidneys, yet pulmonary involvement remains poorly characterized. This study investigated pulmonary structural alterations, IgA deposition, immune cell distribution, and the impact of chronic environmental immune stimulation. Methods: High-IgA (HIGA) mice and BALB/c controls were examined under baseline conditions and following chronic particulate matter (PM) exposure. Histopathology, immunofluorescence, immunohistochemistry, and lectin-based assays were used to assess pulmonary IgA deposition, lymphoid cell aggregation, and immune activation. Results: Compared with BALB/c controls, HIGA mice exhibited pulmonary venular remodeling characterized by thickening of the venular tunica media and IgA deposition within the smooth muscle layer. Under baseline conditions, lymphoid cell aggregation in HIGA mice was predominantly localized to peribronchial regions, whereas IgA deposition and C3a deposition were confined to pulmonary venules with minimal spatial overlap. Following PM exposure, HIGA mice developed additional perivenular lymphoid cell aggregation that spatially corresponded with IgA deposition, whereas BALB/c mice showed predominantly peribronchial aggregation. PM exposure was associated with increased pulmonary Toll-like receptor 9 (TLR9) expression in both strains. In HIGA mice, TLR9-positive immune cells and interleukin-6 (IL6) expression were enriched in perivenular lymphoid cell aggregates. Conclusions: Pulmonary IgA deposition in HIGA mice is associated with vascular remodeling and compartment-specific immune cell distribution, particularly under environmental stimulation. These findings support an association between IgA deposition and localized immune activation in the lung. However, the causal roles of TLR9 and IL6 in this process remain to be determined.
- Blocking Toll-like receptor 9 attenuates bleomycin-induced pulmonary injury
- Badr Alzahrani, Mohamed M. S. Gaballa, Ahmed A. Tantawy, Maha A. Moussa, Salma A. Shoulah, Said M. Elshafae
- J Pathol Transl Med. 2022;56(2):81-91. Published online March 2, 2022
- DOI: https://doi.org/10.4132/jptm.2021.12.27
- 9,262 View
- 156 Download
- 13 Web of Science
- 13 Crossref
-
Abstract
PDF
- Background
Acute respiratory distress syndrome (ARDS) is one of the most common complications in coronavirus disease 2019 patients suffering from acute lung injury (ALI). In ARDS, marked distortion of pulmonary architecture has been reported. The pulmonary lesions in ARDS include hemodynamic derangements (such as alveolar edema and hemorrhage), vascular and bronchiolar damage, interstitial inflammatory cellular aggregations, and eventually fibrosis. Bleomycin induces ARDS-representative pulmonary damage in mice and rats; therefore, we used bleomycin model mice in our study. Recently, Toll-like receptor 9 (TLR9) was implicated in the development of ARDS and ALI.
Methods
In this study, we evaluated the efficiency of a TLR9 blocker (ODN2088) on bleomycin-induced pulmonary damage. We measured the apoptosis rate, inflammatory reaction, and fibroplasia in bleomycin- and bleomycin + ODN2088-treated mice.
Results
Our results showed a significant amelioration in bleomycin-induced damage to pulmonary architecture following ODN2088 treatment. A marked decrease in pulmonary epithelial and endothelial apoptosis rate as measured by cleaved caspase-3 expression, inflammatory reaction as indicated by tumor necrosis factor α expression, and pulmonary fibrosis as demonstrated by Van Gieson staining and α-smooth muscle actin immunohistochemistry were observed following ODN2088 treatment.
Conclusions
All these findings indicate that blocking downstream TLR9 signaling could be beneficial in prevention or mitigation of ARDS through hemodynamic derangements, inflammation, apoptosis, and fibrosis. -
Citations
Citations to this article as recorded by
- Nano-sized DNase scavenges cell-free DNA for acute lung injury treatment
Ruijie Chen, Yitianhe Xu, Zhanzheng Ye, Yixuan Zhu, Mengxue Zhang, Fangfang Lv, Yunzhi Wang, Xinyu Di, Yinhao Lin, Shengnan Song, Zihao Huang, Shize Li, Zhinan He, Hailin Zhang, Longfa Kou
Journal of Controlled Release.2026; 394: 114846. CrossRef - Pharmacological repurposing of cilostazol to attenuate the progression of pulmonary fibrosis: efficacy validation via integrated network pharmacology and in vivo experimentation
Pranaya L. Misar, Kishor V. Otari, Vishal V. Pande, Pradyumna P. Ige
Naunyn-Schmiedeberg's Archives of Pharmacology.2026;[Epub] CrossRef - A novel mouse model of myositis-associated interstitial lung disease was established by using TLR9 agonist combined with muscle homogenate
Ling Bai, Jiarui Zhu, Wenlan Ma, Peipei Zhao, Feifei Li, Cen Zhang, Sigong Zhang
Clinical and Experimental Immunology.2025;[Epub] CrossRef - Toll-like Receptor 9 Inhibition Mitigates Fibroproliferative Responses in Translational Models of Pulmonary Fibrosis
Glenda Trujillo, Alicia Regueiro-Ren, Chunjian Liu, Buqu Hu, Ying Sun, Farida Ahangari, Vitoria Fiorini, Genta Ishikawa, Karam Al Jumaily, Johad Khoury, John McGovern, Chris J. Lee, Xue Yan Peng, Taylor Pivarnik, Huanxing Sun, Anjali Walia, Samuel Woo, Sh
American Journal of Respiratory and Critical Care Medicine.2025; 211(1): 91. CrossRef - CD103+ dendritic cell–fibroblast crosstalk via TLR9, TDO2, and AHR signaling drives lung fibrogenesis
Hannah Carter, Rita Medina Costa, Taylor S. Adams, Talon M. Gilchrist, Claire E. Emch, Monica Bame, Justin M. Oldham, Steven K. Huang, Angela L. Linderholm, Imre Noth, Naftali Kaminski, Bethany B. Moore, Stephen J. Gurczynski
JCI Insight.2025;[Epub] CrossRef - The Mitigated Effect of the Combination of Metformin and Stearic Acid to Ameliorate Bleomycin‐Induced Pulmonary Fibrosis in Rats via Inhibiting Gal‐3/Smad3/α‐SMA and TNF‐α/NF‐κβ Signaling Pathways
Maha M. Salem, Nermin S. Youssef, Mai El Keiy, Abeer A. Khamis
Journal of Biochemical and Molecular Toxicology.2025;[Epub] CrossRef - Unraveling the Interactive Role of Mitochondrial Dysfunction in Promoting Macrophage Polarization in Pulmonary Fibrosis
Jiajia Zou, Junling Jian, Dehua Ge, Bin Zhou, Jiaxiang Zhang
Journal of Biochemical and Molecular Toxicology.2025;[Epub] CrossRef - Mechanisms underlying dose-limiting toxicities of conventional chemotherapeutic agents
Mohammad Amin Manavi, Mohammad Hosein Fathian Nasab, Razieh Mohammad Jafari, Ahmad Reza Dehpour
Journal of Chemotherapy.2024; 36(8): 623. CrossRef - Innate Immune Response-Mediated Inflammation in Viral Pneumonia
Weiwei Ni, Xin Wei, Rui Wu
Journal of Pediatric Infectious Diseases.2024; 19(03): 140. CrossRef - Combination of losartan with pirfenidone: a protective anti-fibrotic against pulmonary fibrosis induced by bleomycin in rats
Arian Amirkhosravi, Maryamossadat Mirtajaddini Goki, Mahmoud Reza Heidari, Somayyeh Karami-Mohajeri, Maryam Iranpour, Maryam Torshabi, Mitra Mehrabani, Ali Mandegary, Mehrnaz Mehrabani
Scientific Reports.2024;[Epub] CrossRef - Suppression of miR-17 Alleviates Acute Respiratory Distress-associated Lung Fibrosis by Regulating Mfn2
Mei-xia Xu, Tao Xu, Ning An
Current Medical Science.2024; 44(5): 964. CrossRef - Study of Recombinant Interleukin-1 Receptor Antagonist Compositions Biological Activity After Injection and Inhalation in Mouse Model of Pulmonary Inflammation
Alexander M. Ischenko, Ksenia A. Nekrasova, Denis S. Laptev, Dmitry V. Bobkov, Alexander A. Kolobov, Andrey S. Simbirtsev
Cytokines and inflammation.2024; 21(3): 153. CrossRef - TLR9: A friend or a foe
Mona M. Saber, Nada Monir, Azza S. Awad, Marwa E. Elsherbiny, Hala F. Zaki
Life Sciences.2022; 307: 120874. CrossRef
- Nano-sized DNase scavenges cell-free DNA for acute lung injury treatment
First
Prev
