An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response
Sang Chul Park1, Hongmin Kim2,3, Yeeun Bak2,3, Dahee Shim3, Kee Woong Kwon3, Chang-Hoon Kim4,5, Joo-Heon Yoon4,5,6, Sung Jae Shin3,6,7
1Department of Otorhinolaryngology-Head and Neck surgery, Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
2Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea
3Brain Korea 21 Program for Leading Universities and Students (PLUS) Project for Medical Science, Yonsei University College of Medicine, Seoul, Korea
4Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea
5The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Korea
6Global Research Laboratory for Allergic Airway Diseases, Seoul, Korea
7Department of Microbiology, Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea
Purpose: Simple and reliable animal models of human diseases contribute to the understanding of disease pathogenesis as well as the development of therapeutic interventions. Although several murine models to mimic human asthma have been established, most of them require anesthesia, resulting in variability among test individuals, and do not mimic asthmatic responses accompanied by T-helper (Th) 17 and neutrophils. As dendritic cells (DCs) are known to play an important role in initiating and maintaining asthmatic inflammation, we developed an asthma model via adoptive transfer of allergen-loaded DCs.
Methods: Ovalbumin (OVA)-loaded bone marrow-derived DCs (BMDCs) (OVA-BMDCs) were injected intravenously 3 times into non-anesthetized C57BL/6 mice after intraperitoneal OVA-sensitization.
Results: OVA-BMDC-transferred mice developed severe asthmatic immune responses when compared with mice receiving conventional OVA challenge intranasally. Notably, remarkable increases in systemic immunoglobulin (Ig) E and IgG1 responses, Th2/Th17-associated cytokines (interleukin [IL]-5, IL-13 and IL-17), Th2/Th17-skewed T-cell responses, and cellular components, including eosinophils, neutrophils, and goblet cells, were observed in the lungs of OVA-BMDC-transferred mice. Moreover, the asthmatic immune responses and severity of inflammation were correlated with the number of OVA-BMDCs transferred, indicating that the disease severity and asthma type may be adjusted according to the experimental purpose by this method. Furthermore, this model exhibited less variation among the test individuals than the conventional model. In addition, this DCs-based asthma model was partially resistant to steroid treatment.
Conclusions: A reliable murine model of asthma by intravenous transfer of OVA-BMDCs was successfully established without anesthesia. This model more accurately reflects heterogeneous human asthma, exhibiting a robust Th2/Th17-skewed response and eosinophilic/neutrophilic infiltration with good reproducibility and low variation among individuals. This model will be useful for understanding the pathogenesis of asthma and would serve as an alternative tool for immunological studies on the function of DCs, T-cell responses and new drugs.