An Alternative Dendritic Cell-Induced Murine Model of Asthma Exhibiting a Robust Th2/Th17-Skewed Response

Abstract

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-BMDCtransferred 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 (i.v.) 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.

Exacerbation of Mycobacterium avium pulmonary infection by comorbid allergic asthma is associated with diminished mycobacterium-specific Th17 responses

“…To quantify airway goblet cells, the following five-point grading system was used: 0, <5% PAS-positive cells; 1, 5–25%; 2, 25–50%; 3, 50–75%; and 4, >75%. Analyses were performed in a blinded manner, and slides were presented in random order for each examination [ 31 , 32 ].…”

“…Serum antigen-specific antibodies were quantified by ELISA as previously described [ 31 ]. Briefly, separated serum was diluted (1:50 for ovalbumin (OVA)-specific IgE and 1:10,000 for OVA-specific IgG1) and added to a plate coated with OVA (2 μg/mL).…”

MicroRNA-21 Inhibition Suppresses Alveolar M2 Macrophages in an Ovalbumin-Induced Allergic Asthma Mice Model

“…Airway inflammation is mediated by not only epithelial cells but also by immune cells such as dendritic cells, T lymphocytes, innate lymphoid cells, and macrophages. 1 2 Traditional pathophysiology of allergic asthma is explained as the Th2 high pathway; however, the roles of pulmonary macrophages in mediating interactions with T cells are emerging.…”

Fms-Like Tyrosine Kinase 3-Independent Dendritic Cells Are Major Mediators of Th2 Immune Responses in Allergen-Induced Asthmatic Mice

“…Furthermore, we established an asthma model via the intravenous (i.v.) transfer of OVA-loaded BMDCs [ 59 ]. Following intraperitoneal OVA sensitization on days 0 and 14, 1 × 10 7 OVA (500 μg)-loaded BMDCs in a total volume of 200 μL were injected i.v.…”