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IL-23 contributes to Particulate Matter induced allergic asthma in the early life of mice and promotes asthma susceptibility

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Abstract

Air pollutant exposure leads to and exacerbates respiratory diseases. Particulate Matter (PM) is a major deleterious factor in the pathophysiology of asthma. Nonetheless, studies on the effects and mechanisms of exposure in the early life of mice remain unresolved. This study aimed to investigate changes in allergic phenotypes and effects on allergen-specific memory T cells resulting from co-exposure of mice in the early life to PM and house dust mites (HDM) and to explore the role of interleukin-23 (IL-23) in this process. PM and low-dose HDM were administered intranasally in 4-day-old C57BL/6 mice. After confirming an increase in IL-23 expression in mouse lung tissues, changes in the asthma phenotype and lung effector/memory Th2 or Th17 cells were evaluated after intranasal administration of anti-IL-23 antibody (Ab) during co-exposure to PM and HDM. Evaluation was performed up to 7 weeks after the last administration. Co-exposure to PM and low-dose HDM resulted in increases in airway hyperresponsiveness (AHR), eosinophils, neutrophils, and persistent Th2/Th17 effector/memory cells, which were all inhibited by anti-IL-23 Ab administration. When low-dose HDM was administered twice after a 7-week rest, mice exposed to PM and HDM during the previous early life period exhibited re-increases AHR, eosinophil count, HDM-specific IgG1, and effector/memory Th2 and Th17 cell populations. However, anti-IL-23 Ab administration during the early life period resulted in inhibition. Co-exposure to PM and low-dose HDM reinforced the allergic phenotypes and allergen-specific memory responses in early life of mice. During this process, IL-23 contributes to the enhancement of effector/memory Th2/Th17 cells and allergic phenotypes.

Graphical Abstract

Exposure of Particulate Matter (PM) and a low dose of HDM in mice of early life period induces the expression of IL-23 from CD11c + cells and airway epithelial cells, AHR, eosinophils, neutrophils, effector/memory Th2 and Th17 cells in lung tissue. These changes decreased when anti-IL-23 Ab was administered. When low-dose HDM was administered twice after 7 weeks of rest, mice exposed to PM and HDM during the previous early life period had re-increases in allergic responses, effector/memory Th2, and Th17 cells. The administration of anti-IL-23 Ab in the previous early life period showed their inhibition. HDM, house dust mite; AHR, airway hyperresponsiveness; anti-IL-23 Ab; anti-IL-23 antibody

Key messages

  • PM-induced IL-23 expression, allergic responses in HDMinstilled mice of early life period.

  • PM-induced effector/memory Th2/Th17 cells in HDMinstilled mice of early life period.

  • Inhibition of IL-23 reduced the increase in allergic responses.

  • Inhibition of IL-23 reduced the increase in allergic responses.

  • After the resting period, HDM administration showed re-increase in allergic responses.

  • Inhibition of IL-23 reduced the HDM-recall allergic responses.

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Data availability

All data have been reported.

Abbreviations

PM:

Particulate Matter

HDM:

House dust mite

Dp:

Dermatophagoides pteronyssinus

IL-23:

Interleukin-23

Th2:

T helper 2

Th17:

T helper 17

Epcam:

Epithelial cell adhesion molecule

DC:

Dendritic cell

BMDC:

Bone marrow dendritic cell

Anti IL-23:

Anti IL-23 antibody

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Funding

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (NRF-2019R1A2C4070214) and the SNUH Research Fund (grant no. 04–2022-0690).

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea

    Heung-Woo Park

  2. Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea

    Heung-Woo Park

  3. Institute of Allergy and Clinical Immunology, Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-Ro, Jongno-Gu, Seoul, 110-744, Republic of Korea

    Hyun Seung Lee

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Contributions

PHW: designed the experiments, analyzed the data, constructed the figures, drafted the manuscript. LHS: designed the experiments, performed experiments, performed the assays, analyzed the data, constructed the figures, drafted the manuscript. All authors read and approved the manuscript.

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Correspondence to Hyun Seung Lee.

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The experimental protocol was approved by the Institutional Animal Care and Use Committee of the Institute of Laboratory Animal Resources at Seoul National University Hospital.

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Park, HW., Lee, H.S. IL-23 contributes to Particulate Matter induced allergic asthma in the early life of mice and promotes asthma susceptibility. J Mol Med 102, 129–142 (2024). https://doi.org/10.1007/s00109-023-02393-6

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  • DOI: https://doi.org/10.1007/s00109-023-02393-6

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