Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs
We previously demonstrated that fetal allergen exposure caused T-helper 2 (Th2) cell sensitization. Although neonates are immunologically more mature than fetuses, asthmatic lungs were reportedly mitigated by neonatal allergen administration, mechanically referring to regulatory T-cells and TGF-<...
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MDPI AG
2021-06-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/9/6/688 |
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| author | Jeng-Chang Chen Cheng-Chi Chan Nai-Chun Ting Ming-Ling Kuo |
| author_facet | Jeng-Chang Chen Cheng-Chi Chan Nai-Chun Ting Ming-Ling Kuo |
| author_sort | Jeng-Chang Chen |
| collection | DOAJ |
| description | We previously demonstrated that fetal allergen exposure caused T-helper 2 (Th2) cell sensitization. Although neonates are immunologically more mature than fetuses, asthmatic lungs were reportedly mitigated by neonatal allergen administration, mechanically referring to regulatory T-cells and TGF-<i>β</i> signaling but lacking the immunological profiles after neonatal exposure. To reappraise the immunological outcome of neonatal allergen exposure, we injected adjuvant-free ovalbumin intraperitoneally into 2-day-old BALB/c neonates, followed by aerosolized ovalbumin inhalation in adulthood. Mice were examined for the immunological profiles specifically after neonatal exposures, lung function and histology (hematoxylin-eosin or periodic acid Schiff staining), and gene expressions of intrapulmonary cytokines (IL-4, IL-5, IL-13 and IFN-γ) and chemokines (CCL17, CCL22, CCL11 and CCL24). Neonatal ovalbumin exposure triggered Th2-skewed sensitization and ovalbumin-specific IgE production. Subsequent ovalbumin inhalation in adulthood boosted Th2 immunity and caused asthmatic lungs with structural and functional alterations of airways. Gender difference mainly involved airway hyperresponsiveness and resistance with greater female susceptibility to methacholine bronchospastic stimulation. In lungs, heightened chemoattractant gene expressions were only granted to neonatally ovalbumin-sensitized mice with aerosolized ovalbumin stress in adulthood, and paralleled by upregulated Th2 cytokine genes. Thus, aeroallergen stress in atopic individuals might upregulate the expression of intrapulmonary chemoattractants to recruit Th2 cells and eosinophils into the lungs, pathogenically linked to asthma development. Conclusively, murine neonates were sensitive to allergen exposures. Exposure events during neonatal stages were crucial to asthma predisposition in later life. These findings from a murine model point to allergen avoidance in neonatal life, possibly even very early in utero, as the best prospect of primary asthma prevention. |
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| language | English |
| last_indexed | 2024-03-10T10:17:58Z |
| publishDate | 2021-06-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-cd477c280aab4d0abd1b207d23452a112023-11-22T00:42:28ZengMDPI AGBiomedicines2227-90592021-06-019668810.3390/biomedicines9060688Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic LungsJeng-Chang Chen0Cheng-Chi Chan1Nai-Chun Ting2Ming-Ling Kuo3Department of Surgery, Chang Gung Children’s Hospital, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanAbnova Corporation, Taipei 114, TaiwanGraduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanDepartment of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, TaiwanWe previously demonstrated that fetal allergen exposure caused T-helper 2 (Th2) cell sensitization. Although neonates are immunologically more mature than fetuses, asthmatic lungs were reportedly mitigated by neonatal allergen administration, mechanically referring to regulatory T-cells and TGF-<i>β</i> signaling but lacking the immunological profiles after neonatal exposure. To reappraise the immunological outcome of neonatal allergen exposure, we injected adjuvant-free ovalbumin intraperitoneally into 2-day-old BALB/c neonates, followed by aerosolized ovalbumin inhalation in adulthood. Mice were examined for the immunological profiles specifically after neonatal exposures, lung function and histology (hematoxylin-eosin or periodic acid Schiff staining), and gene expressions of intrapulmonary cytokines (IL-4, IL-5, IL-13 and IFN-γ) and chemokines (CCL17, CCL22, CCL11 and CCL24). Neonatal ovalbumin exposure triggered Th2-skewed sensitization and ovalbumin-specific IgE production. Subsequent ovalbumin inhalation in adulthood boosted Th2 immunity and caused asthmatic lungs with structural and functional alterations of airways. Gender difference mainly involved airway hyperresponsiveness and resistance with greater female susceptibility to methacholine bronchospastic stimulation. In lungs, heightened chemoattractant gene expressions were only granted to neonatally ovalbumin-sensitized mice with aerosolized ovalbumin stress in adulthood, and paralleled by upregulated Th2 cytokine genes. Thus, aeroallergen stress in atopic individuals might upregulate the expression of intrapulmonary chemoattractants to recruit Th2 cells and eosinophils into the lungs, pathogenically linked to asthma development. Conclusively, murine neonates were sensitive to allergen exposures. Exposure events during neonatal stages were crucial to asthma predisposition in later life. These findings from a murine model point to allergen avoidance in neonatal life, possibly even very early in utero, as the best prospect of primary asthma prevention.https://www.mdpi.com/2227-9059/9/6/688neonatechemokinecytokinesensitizationovalbuminasthma |
| spellingShingle | Jeng-Chang Chen Cheng-Chi Chan Nai-Chun Ting Ming-Ling Kuo Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs Biomedicines neonate chemokine cytokine sensitization ovalbumin asthma |
| title | Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs |
| title_full | Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs |
| title_fullStr | Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs |
| title_full_unstemmed | Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs |
| title_short | Allergen Exposure in Murine Neonates Promoted the Development of Asthmatic Lungs |
| title_sort | allergen exposure in murine neonates promoted the development of asthmatic lungs |
| topic | neonate chemokine cytokine sensitization ovalbumin asthma |
| url | https://www.mdpi.com/2227-9059/9/6/688 |
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