Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses
| Autor: | Cheng-Chi Chan, Liang-Shiou Ou, Chia-Jen Wu, Hsiu-Yueh Yu, Ming-Ling Kuo, Hsueh-Ling Chang, Jeng-Chang Chen, Li-Yun Tseng |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Pulmonary and Respiratory Medicine Ovalbumin Antigen presentation Mice Transgenic Critical Care and Intensive Care Medicine Mice 03 medical and health sciences Th2 Cells 0302 clinical medicine Immune system Antigen Pregnancy Immunity Respiratory Hypersensitivity Animals Medicine Macrophage Sensitization Mice Inbred BALB C Phagocytes biology business.industry Allergens respiratory system medicine.disease 030104 developmental biology medicine.anatomical_structure Prenatal Exposure Delayed Effects Immunology biology.protein Female business Anaphylaxis 030215 immunology |
| Zdroj: | American Journal of Respiratory and Critical Care Medicine. 194:934-947 |
| ISSN: | 1535-4970 1073-449X |
| Popis: | Actively acquired tolerance occurs when foreign antigens come into contact with the immature fetal immune system.Armed with the knowledge of actively acquired tolerance, we attempted to prenatally abolish or diminish allergic responses.In utero injection of adjuvant-free ovalbumin (OVA) was conducted in Gestational Day 14 FVB/N mouse fetuses. Postnatally, mice were evaluated for their resistance to intraperitoneal OVA sensitization and oral or aerosolized OVA challenge, and then they were examined for humoral and cellular immunological profiles, airway hyperresponsiveness to bronchospastic stimuli, and lung histology. Fluorescent conjugates of OVA were used for further studies of mechanisms.This presumed tolerogenic action turned out to be a sensitization process with the development of anaphylaxis or heightened recall, T-helper cell type 2-skewed responses to postnatal encounter with OVA. Further postnatal aerosolized OVA stress triggered allergic lungs with functional and structural alterations of airways. The unintended consequence resulted from macrophage-like fetal phagocytes that took up OVA and differentiated toward dendritic cells. These fetal dendritic cell progenitors attenuated proteolysis of endocytosed OVA for delayed presentation in postnatal life. This specialty of fetal phagocytes effectively retains the memory of antigens internalized early before full development of the immune system, leading to an event of in utero sensitization.Our results have mechanical implications for prenatal imprinting of atopy and shed light on the importance of fetal phagocytes in shaping the developing immune system and initiating allergic airway diseases. |
| Databáze: | OpenAIRE |
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