Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

Sohvi Ohtonen; Henna Jäntti; Luca Giudice; Ahmed Mohamed; Anastasia Shakirzyanova; Táňa Závodná; Ilya Belevich; Hong Yan; Angélica María Sabogal-Guáqueta; Liudmila Saveleva; Mari Anna Väänänen; Ashley Rillo-Albert; Elisa Perciballi; Daniela Ferrari; Minna Mari Tervo; Mireia Gómez-Budia; Zdeněk Krejčík; Päivi Aakko-Saksa; Jari Koistinaho; Šárka Lehtonen; Katja M. Kanninen; Jan Topinka; Eija Jokitalo; Alejandra Sierra; Martina Schmidt; Amalia M. Dolga; Pasi I. Jalava; Paula Korhonen; Tarja Malm

doi:10.1016/j.envint.2025.109467

Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

Sohvi Ohtonen^*, Henna Jäntti, Luca Giudice, Ahmed Mohamed, Anastasia Shakirzyanova, Táňa Závodná, Ilya Belevich, Hong Yan, Angélica María Sabogal-Guáqueta, Liudmila Saveleva, Mari Anna Väänänen, Ashley Rillo-Albert, Elisa Perciballi, Daniela Ferrari, Minna Mari Tervo, Mireia Gómez-Budia, Zdeněk Krejčík, Päivi Aakko-Saksa, Jari Koistinaho, Šárka LehtonenKatja M. Kanninen, Jan Topinka, Eija Jokitalo, Alejandra Sierra, Martina Schmidt, Amalia M. Dolga, Pasi I. Jalava, Paula Korhonen, Tarja Malm

^*Corresponding author for this work

BA5208 Catalytic processes

Research output: Contribution to journal › Article › Scientific › peer-review

Abstract

Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.

Original language	English
Article number	109467
Journal	Environment International
Volume	199
DOIs	https://doi.org/10.1016/j.envint.2025.109467
Publication status	Published - May 2025
MoE publication type	A1 Journal article-refereed

Funding

We thank all the individuals for donating valuable samples and people involved in the provision and generation of iPSC lines. We thank Prof Alice P\u00E9bay (The University of Melbourne) for providing the iPSC lines MBE2960 and MBE2968. This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 814978 (TUBE: Transport-derived ultrafines and the brain effects), the European Union's Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie agreement No 101034307 and Research Council of Finland under grant agreement No 334800. This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (the Research Infrastructure NanoEnviCZ, LM2023066) and the European Union - European Structural and Investments Funds in the frame of Operational Programme Research Development and Education - project Pro-NanoEnviCz (Project No. CZ.02.1.01/0.0/0.0/16_013/0001821). This research has been supported by funding from P\u00E4ivikki and Sakari Sohlberg Foundation. We thank the University of Eastern Finland Doctoral Programme in Molecular Medicine (DPMM). Part of the work was carried out with the support of UEF Cell and Tissue Imaging Unit, University of Eastern Finland, Biocenter Kuopio and EuroBioimaging Finland, and In vitro and ex vivo electrophysiology core facility, University of Eastern Finland. We thank Taina Suntio and Mervi Lindman, Electron Microscopy Unit, University of Helsinki for technical assistance with EM sample preparation and Biocenter Finland for EM imaging infrastructure support. We thank Laura Mussalo for her assistance with pollutant dosing and exposure. We thank all the individuals for donating valuable samples and people involved in the provision and generation of iPSC lines. We thank Prof Alice P\u00E9bay (The University of Melbourne) for providing the iPSC lines MBE2960 and MBE2968 . This project has received funding from the European Union's Horizon 2020 research and innovation program under grant agreement No 814978 (TUBE: Transport-derived ultrafines and the brain effects), the European Union\u2019s Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie agreement No 101034307 and Research Council of Finland under grant agreement No 334800. This work was supported by the Ministry of Education, Youth and Sports of the Czech Republic (the Research Infrastructure NanoEnviCZ, LM2023066) and the European Union - European Structural and Investments Funds in the frame of Operational Programme Research Development and Education - project Pro-NanoEnviCz (Project No. CZ.02.1.01/0.0/0.0/16_013/0001821). This research has been supported by funding from P\u00E4ivikki and Sakari Sohlberg Foundation. We thank the University of Eastern Finland Doctoral Programme in Molecular Medicine (DPMM).

Keywords

Air pollution
Diesel
Human microglia
iPSC
Lysosome

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Ohtonen, S., Jäntti, H., Giudice, L., Mohamed, A., Shakirzyanova, A., Závodná, T., Belevich, I., Yan, H., Sabogal-Guáqueta, A. M., Saveleva, L., Väänänen, M. A., Rillo-Albert, A., Perciballi, E., Ferrari, D., Tervo, M. M., Gómez-Budia, M., Krejčík, Z., Aakko-Saksa, P., Koistinaho, J., ... Malm, T. (2025). Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia. Environment International, 199, Article 109467. https://doi.org/10.1016/j.envint.2025.109467

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title = "Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia",

abstract = "Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.",

keywords = "Air pollution, Diesel, Human microglia, iPSC, Lysosome",

author = "Sohvi Ohtonen and Henna J{\"a}ntti and Luca Giudice and Ahmed Mohamed and Anastasia Shakirzyanova and T{\'a}{\v n}a Z{\'a}vodn{\'a} and Ilya Belevich and Hong Yan and Sabogal-Gu{\'a}queta, {Ang{\'e}lica Mar{\'i}a} and Liudmila Saveleva and V{\"a}{\"a}n{\"a}nen, {Mari Anna} and Ashley Rillo-Albert and Elisa Perciballi and Daniela Ferrari and Tervo, {Minna Mari} and Mireia G{\'o}mez-Budia and Zden{\v e}k Krej{\v c}{\'i}k and P{\"a}ivi Aakko-Saksa and Jari Koistinaho and {\v S}{\'a}rka Lehtonen and Kanninen, {Katja M.} and Jan Topinka and Eija Jokitalo and Alejandra Sierra and Martina Schmidt and Dolga, {Amalia M.} and Jalava, {Pasi I.} and Paula Korhonen and Tarja Malm",

note = "Publisher Copyright: {\textcopyright} 2025 The Author(s)",

year = "2025",

month = may,

doi = "10.1016/j.envint.2025.109467",

language = "English",

volume = "199",

journal = "Environment International",

issn = "0160-4120",

publisher = "Elsevier",

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Ohtonen, S, Jäntti, H, Giudice, L, Mohamed, A, Shakirzyanova, A, Závodná, T, Belevich, I, Yan, H, Sabogal-Guáqueta, AM, Saveleva, L, Väänänen, MA, Rillo-Albert, A, Perciballi, E, Ferrari, D, Tervo, MM, Gómez-Budia, M, Krejčík, Z, Aakko-Saksa, P, Koistinaho, J, Lehtonen, Š, Kanninen, KM, Topinka, J, Jokitalo, E, Sierra, A, Schmidt, M, Dolga, AM, Jalava, PI, Korhonen, P & Malm, T 2025, 'Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia', Environment International, vol. 199, 109467. https://doi.org/10.1016/j.envint.2025.109467

TY - JOUR

T1 - Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

AU - Ohtonen, Sohvi

AU - Jäntti, Henna

AU - Giudice, Luca

AU - Mohamed, Ahmed

AU - Shakirzyanova, Anastasia

AU - Závodná, Táňa

AU - Belevich, Ilya

AU - Yan, Hong

AU - Sabogal-Guáqueta, Angélica María

AU - Saveleva, Liudmila

AU - Väänänen, Mari Anna

AU - Rillo-Albert, Ashley

AU - Perciballi, Elisa

AU - Ferrari, Daniela

AU - Tervo, Minna Mari

AU - Gómez-Budia, Mireia

AU - Krejčík, Zdeněk

AU - Aakko-Saksa, Päivi

AU - Koistinaho, Jari

AU - Lehtonen, Šárka

AU - Kanninen, Katja M.

AU - Topinka, Jan

AU - Jokitalo, Eija

AU - Sierra, Alejandra

AU - Schmidt, Martina

AU - Dolga, Amalia M.

AU - Jalava, Pasi I.

AU - Korhonen, Paula

AU - Malm, Tarja

PY - 2025/5

Y1 - 2025/5

N2 - Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.

AB - Exposure to air pollution is associated with neurological diseases. Traffic is a major source of air pollution, consisting of a complex mixture of ultrafine particles, that can invade the brain and induce a microglia-mediated inflammatory response. However, the exact mechanisms of how traffic-related particles impact human microglia remain poorly understood. This study investigates the effects of diesel exhaust particles (DEPs) on human induced pluripotent stem cell-derived microglia-like cells (iMGL). We exposed iMGLs to three different DEPs and studied the impact on the iMGL transcriptome and functionality, focusing on cytokine secretion, mitochondrial respiration, lysosomal function, and phagocytosis. A20 particles were collected from a heavy-duty engine run with petroleum diesel. For A0, the same engine was run with renewable diesel. E6 was produced with a modern 2019 model diesel passenger car run with renewable diesel. RNAseq revealed activation of the cytokine storm pathway and inhibition of the autophagy pathway in iMGLs after exposure to particles derived from older diesel emission technology (A20, A0). Particles from the modern diesel engine technology (E6) did not alter microglial transcriptome after 24 h exposure. A20 and A0 exposure led to impaired lysosomal functions in iMGLs. In contrast, E6 did not cause major alterations in microglia functions. In addition, we show that response to particles is more pronounced in human iMGLs compared to mouse primary microglia. To conclude, particles from older emission technology impair phago-lysosomal functions of iMGLs, but modern alternatives with filtration do not induce drastic changes in the functionality of iMGLs.

KW - Air pollution

KW - Diesel

KW - Human microglia

KW - iPSC

KW - Lysosome

UR - http://www.scopus.com/inward/record.url?scp=105004552541&partnerID=8YFLogxK

U2 - 10.1016/j.envint.2025.109467

DO - 10.1016/j.envint.2025.109467

M3 - Article

AN - SCOPUS:105004552541

SN - 0160-4120

VL - 199

JO - Environment International

JF - Environment International

M1 - 109467

ER -

Traffic-related diesel pollution particles impair the lysosomal functions of human iPSC-derived microglia

Abstract

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Keywords

UN SDGs

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