The Therapeutic Potential of Farm Dust Extracts in a Mouse Model of Eosinophilic Inflammation
Asthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protect...
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| Vydané v: | Allergy (Copenhagen) |
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| Hlavní autori: | , , , , , , , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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Denmark
22.10.2025
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| ISSN: | 0105-4538, 1398-9995, 1398-9995 |
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| Abstract | Asthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.
We used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.
FDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.
FDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy. |
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| AbstractList | Asthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.BACKGROUNDAsthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach.We used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.METHODSWe used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors.FDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.RESULTSFDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis.FDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy.CONCLUSIONFDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy. Asthma affects over 355 million people globally and poses a major healthcare burden. While corticosteroids remain a cornerstone of treatment, their side effects highlight the need for additional therapeutic strategies. Environmental exposures such as traditional farm dust have been linked to protection against asthma and allergies. This study investigated the therapeutic potential of farm dust extract (FDE) in a murine model of allergic asthma when administered after sensitization and during allergen challenge, mimicking a secondary prevention or early interventional treatment approach. We used an ovalbumin (OVA)-induced asthma model to evaluate FDE effects on airway eosinophilia, airway hyperresponsiveness (AHR), mucus production, and IgE levels. Mechanistic studies assessed regulatory T cells (Tregs), dendritic cell phenotype, epithelial barrier integrity, and cytokine signaling. Complementary experiments were performed in peripheral blood mononuclear cells (PBMCs) from asthmatic donors. FDE significantly reduced airway inflammation and AHR, with secondary prevention effects comparable to systemic dexamethasone. FDE enhanced Treg frequency and CTLA-4 expression, modulated dendritic cell MHC-II and PD-L1 expression, and promoted an immunoregulatory environment. It also restored epithelial barrier integrity and increased IL-33 release, supporting Treg activation. In asthmatic PBMCs, FDE increased Tregs, reduced Th2 cells, and suppressed CIITA, suggesting similar immune-regulatory effects. Interactions among IL-33, amphiregulin (AREG), and Tregs highlighted a mechanism reinforcing immune-epithelial homeostasis. FDE administered after sensitization and during allergen challenge mitigated key asthma features in mice and showed translational potential in human cells, supporting its development as a novel, environmentally derived immunomodulatory strategy. |
| Author | Ragab, Mohab Korkmaz, Rabia Ülkü Müller, Christoph Kapellos, Theodore S. Nawroth, Janna Ertüz, Zeynep Rankl, Bettina Chen, Sirui Augustin, Romina Yildirim, Ali Önder Tan, Xiaomei Dragunas, Guilherme Shankhwar, Soni Omony, Jimmy von Mutius, Erika Klotz, Markus Jeridi, Aicha |
| Author_xml | – sequence: 1 givenname: Rabia Ülkü orcidid: 0000-0002-2566-5346 surname: Korkmaz fullname: Korkmaz, Rabia Ülkü organization: Helmholtz Zentrum München, Research Center for Environmental Health Institute of Asthma and Allergy Prevention Neuherberg Germany – sequence: 2 givenname: Jimmy surname: Omony fullname: Omony, Jimmy organization: Helmholtz Zentrum München, Research Center for Environmental Health Institute of Asthma and Allergy Prevention Neuherberg Germany – sequence: 3 givenname: Xiaomei surname: Tan fullname: Tan, Xiaomei organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany – sequence: 4 givenname: Markus surname: Klotz fullname: Klotz, Markus organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany – sequence: 5 givenname: Guilherme orcidid: 0000-0001-6560-8402 surname: Dragunas fullname: Dragunas, Guilherme organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany – sequence: 6 givenname: Sirui surname: Chen fullname: Chen, Sirui organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany – sequence: 7 givenname: Soni surname: Shankhwar fullname: Shankhwar, Soni organization: Helmholtz Zentrum München, Research Center for Environmental Health Institute of Asthma and Allergy Prevention Neuherberg Germany – sequence: 8 givenname: Zeynep surname: Ertüz fullname: Ertüz, Zeynep organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany – sequence: 9 givenname: Christoph surname: Müller fullname: Müller, Christoph organization: Department of Pharmacy—Center for Drug Research Ludwig‐Maximilians Universität München Munich Germany – sequence: 10 givenname: Mohab surname: Ragab fullname: Ragab, Mohab organization: Department of Internal Medicine II, TUM University Hospital, Klinikum Rechts der Isar, TUM School of Medicine and Health Technical University of Munich Munich Germany – sequence: 11 givenname: Aicha surname: Jeridi fullname: Jeridi, Aicha organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany, German Center for Lung Research (DZL) Munich Germany – sequence: 12 givenname: Romina surname: Augustin fullname: Augustin, Romina organization: German Center for Lung Research (DZL) Munich Germany, Helmholtz Pioneer Campus Helmholtz Zentrum München Neuherberg Germany, Institute of Biological and Medical Imaging Bioengineering Center, Helmholtz Zentrum München Neuherberg Germany, Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health Technical University of Munich Munich Germany, Faculty of Engineering Sciences University of Heidelberg Heidelberg Germany – sequence: 13 givenname: Janna surname: Nawroth fullname: Nawroth, Janna organization: German Center for Lung Research (DZL) Munich Germany, Helmholtz Pioneer Campus Helmholtz Zentrum München Neuherberg Germany, Institute of Biological and Medical Imaging Bioengineering Center, Helmholtz Zentrum München Neuherberg Germany, Chair of Biological Imaging at the Central Institute for Translational Cancer Research (TranslaTUM), School of Medicine and Health Technical University of Munich Munich Germany – sequence: 14 givenname: Theodore S. surname: Kapellos fullname: Kapellos, Theodore S. organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany, German Center for Lung Research (DZL) Munich Germany, Institute of Experimental Pneumology, LMU University Hospital Ludwig‐Maximilian's University Munich Germany – sequence: 15 givenname: Bettina surname: Rankl fullname: Rankl, Bettina organization: Helmholtz Zentrum München, Research Center for Environmental Health Institute of Asthma and Allergy Prevention Neuherberg Germany – sequence: 16 givenname: Ali Önder orcidid: 0000-0003-1969-480X surname: Yildirim fullname: Yildirim, Ali Önder organization: Comprehensive Pneumology Center (CPC‐M) Institute of Lung Health and Immunity (LHI), Helmholtz Munich Munich Germany, German Center for Lung Research (DZL) Munich Germany, Institute of Experimental Pneumology, LMU University Hospital Ludwig‐Maximilian's University Munich Germany – sequence: 17 givenname: Erika surname: von Mutius fullname: von Mutius, Erika organization: Helmholtz Zentrum München, Research Center for Environmental Health Institute of Asthma and Allergy Prevention Neuherberg Germany, German Center for Lung Research (DZL) Munich Germany, Ludwig‐Maximilians University Dr. von Hauner Children's Hospital Munich Germany |
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| Keywords | regulatory T cells prophylactic intervention asthma epithelial barrier Th2 inflammation farm dust extract |
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