title: Fetal Phagocytes Take up Allergens to Initiate T-Helper Cell Type 2 Immunity and Facilitate Allergic Airway Responses.
abstract: 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.
authors.affiliation: 1 Department of Surgery.|2 Graduate Institute of Clinical Medical Sciences and.
authors.forename: Jeng-Chang
authors.identifier: 0000-0002-7776-4338
authors.initials: JC
authors.lastname: Chen
authors.affiliation: 3 Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; and.
authors.forename: Cheng-Chi
authors.initials: CC
authors.lastname: Chan
authors.affiliation: 3 Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; and.
authors.forename: Chia-Jen
authors.initials: CJ
authors.lastname: Wu
authors.affiliation: 4 Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, and.
authors.forename: Liang-Shiou
authors.initials: LS
authors.lastname: Ou
authors.affiliation: 5 Pediatric Research Center, Chang Gung Children's Hospital, Taoyuan, Taiwan.
authors.forename: Hsiu-Yueh
authors.initials: HY
authors.lastname: Yu
authors.affiliation: 5 Pediatric Research Center, Chang Gung Children's Hospital, Taoyuan, Taiwan.
authors.forename: Hsueh-Ling
authors.initials: HL
authors.lastname: Chang
authors.affiliation: 5 Pediatric Research Center, Chang Gung Children's Hospital, Taoyuan, Taiwan.
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Tseng
authors.affiliation: 4 Division of Allergy, Asthma and Rheumatology, Department of Pediatrics, and.|3 Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan; and.|6 Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Ming-Ling
authors.initials: ML
authors.lastname: Kuo
mesh_terms: D000485:Allergens / Q000276:immunology*; D000818:Animals; D005260:Female; D051379:Mice / Q000196:embryology; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000276:immunology; D010586:Phagocytes / Q000276:immunology* / Q000502:physiology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000196:embryology / Q000276:immunology* / Q000503:physiopathology; D018418:Th2 Cells / Q000276:immunology* / Q000502:physiology
chemical_list: D000485:Allergens; D010047:Ovalbumin
keywords: allergic airway disease; antigen presentation; dendritic cell progenitor; in utero sensitization; macrophage