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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Inflammation
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1495581
This article is part of the Research Topic Community Series in Inflammation in Respiratory and Neurological Diseases and the immune-interaction of the lung-brain axis: Volume II View all 10 articles

Aspirin-Triggered Resolvin D1 Modulates Pulmonary and Neurological Inflammation in an IL-22 Knock-Out Organic Dust Exposure Mouse Model

Provisionally accepted
Alissa Nicole Threatt Alissa Nicole Threatt 1Jade White Jade White 1,2*Nathan Klepper Nathan Klepper 1,3*Zachary Brier Zachary Brier 1,4*Logan S. Dean Logan S. Dean 1,5*Ash Ibarra Ash Ibarra 1,6*Macallister Harris Macallister Harris 7*Kaylee Jones Kaylee Jones 1*Mäelis J.L. Wahl Mäelis J.L. Wahl 1,8*Melea Barahona Melea Barahona 1,5*Emmanuel O. Oyewole Emmanuel O. Oyewole 1,9*Morgan Pauly Morgan Pauly 4*Julie Ann Moreno Julie Ann Moreno 1*Tara Nordgren Tara Nordgren 1*
  • 1 Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States
  • 2 Department of Biology, College of Natural Sciences, Colorado State University, Fort Collins, Colorado, United States
  • 3 Department of Animal Sciences, College of Agricultural Sciences, Colorado State University, Fort Collins, Colorado, United States
  • 4 Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, United States
  • 5 Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, California, United States
  • 6 Department of Chemistry, College of Natural Sciences, Colorado State University, Fort Collins, Colorado, United States
  • 7 Experimental Pathology Facility, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
  • 8 Department of Biochemistry and Molecular Biology, College of Natural Sciences, Colorado State University, Fort Collins, Colorado, United States
  • 9 Toxicology Graduate Program, Colorado State University, Fort Collins, California, United States

The final, formatted version of the article will be published soon.

    Agriculture dust contains many organic immunogenic compounds, and organic dust exposure is strongly associated with the development of immune-mediated chronic pulmonary diseases such as chronic obstructive pulmonary disease (COPD). Chronic organic dust exposure from agriculture sources induces chronic lung inflammatory diseases and organic dust exposure has recently been linked to an increased risk of developing dementia. The cytokine interleukin-22 (IL-22) has been established as an important mediator in the resolution and repair of lung tissues. The omega-3 fatty acid metabolite aspirin-triggered Resolvin D1 (AT-RvD1) has shown efficacy in modulating the immune response in both pulmonary and neurological inflammation but has not been explored as a therapeutic in organic dust exposure-induced neuroinflammation. Investigating the link between IL-22 and AT-RvD1 may help in developing effective therapies for these immune-mediated diseases. We aimed to investigate the link between organic dust exposure and neuroinflammation, the role of IL-22 in the pulmonary and neurological immune response to organic dust exposure, and the immune-modulating therapeutic applications of AT-RvD1 in an IL-22 knock-out mouse model of organic dust exposure. C57BL/6J (WT) and IL-22 knock-out (KO) mice were repetitively exposed to aqueous agriculture organic dust extract (DE) 5 days per week for 3 weeks (15 total instillations) and treated with AT-RvD1 either once per week (3 total injections) or 5 times per week (15 total injections) for 3 weeks and allowed to recover for 3 days. We observed a significant pulmonary and neurological immune response to DE characterized by the development of inducible bronchus associated lymphoid tissue in the lung and gliosis in the frontal areas of the brain. We also observed that IL-22 knock-out increased pulmonary and neurological inflammation severity. Animals exposed to DE and treated with AT-RvD1 displayed reduced lung pathology severity and gliosis. Our data demonstrate that DE exposure contributes to neurological inflammation and that IL-22 is crucial to effective tissue repair processes. Our data further suggest that AT-RvD1 may have potential as a novel therapeutic for organic dust exposure-induced, immune-mediated pulmonary and neurological inflammation, improving outcomes of those with these diseases.

    Keywords: agriculture dust, lung inflammation, Neuroinflammation, Omega-3 fatty Acids, SPM, Aspirin-triggered resolvin D1, AT-RvD1

    Received: 12 Sep 2024; Accepted: 19 Nov 2024.

    Copyright: © 2024 Threatt, White, Klepper, Brier, Dean, Ibarra, Harris, Jones, Wahl, Barahona, Oyewole, Pauly, Moreno and Nordgren. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jade White, Department of Biology, College of Natural Sciences, Colorado State University, Fort Collins, 80523, Colorado, United States
    Nathan Klepper, Department of Animal Sciences, College of Agricultural Sciences, Colorado State University, Fort Collins, 80523-1171, Colorado, United States
    Zachary Brier, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, 80523-1680, Colorado, United States
    Logan S. Dean, Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, California, United States
    Ash Ibarra, Department of Chemistry, College of Natural Sciences, Colorado State University, Fort Collins, 80523-1872, Colorado, United States
    Macallister Harris, Experimental Pathology Facility, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, United States
    Kaylee Jones, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, 80523-1681, Colorado, United States
    Mäelis J.L. Wahl, Department of Biochemistry and Molecular Biology, College of Natural Sciences, Colorado State University, Fort Collins, 80523-1801, Colorado, United States
    Melea Barahona, Cell and Molecular Biology Graduate Program, Colorado State University, Fort Collins, California, United States
    Emmanuel O. Oyewole, Toxicology Graduate Program, Colorado State University, Fort Collins, California, United States
    Morgan Pauly, Department of Biomedical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, 80523-1680, Colorado, United States
    Julie Ann Moreno, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, 80523-1681, Colorado, United States
    Tara Nordgren, Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, 80523-1681, Colorado, United States

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