Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model
| Autor: | Yasuyuki Negishi, Hidemi Takahashi, Kimihiro Okubo, Yohko Nakagawa, Ayako Wakabayashi, Masumi Shimizu, Takachika Hiroi, Ryosuke Murakami |
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| Rok vydání: | 2015 |
| Předmět: |
Allergy
Ovalbumin Immunology Primary Cell Culture chemical and pharmacologic phenomena Cell Count Galactosylceramides Th1 polarization Histamine Release Severity of Illness Index Sneezing Mice Immune system Th2 Cells medicine Immunology and Allergy Animals Humans Cell Lineage Mast Cells Mice Inbred BALB C Follicular dendritic cells business.industry hemic and immune systems General Medicine Dendritic cell Dendritic Cells Immunoglobulin E Th1 Cells medicine.disease Rhinitis Allergic Disease Models Animal Immunoglobulin G Alum Compounds Female Airway business Bronchoalveolar Lavage Fluid Injections Intraperitoneal |
| Zdroj: | International archives of allergy and immunology. 168(4) |
| ISSN: | 1423-0097 |
| Popis: | Background: Two major distinct subsets of dendritic cells (DCs) are arranged to regulate immune responses: DEC-205+ DCs drive Th1 polarization and 33D1+ DCs establish Th2 dominancy. Th1 polarization can be achieved either by depletion of 33D1+ DCs with a 33D1-specific monoclonal antibody (mAb) or by activation of DEC-205+ DCs via intraperitoneal injection of α-galactosylceramide (α-GalCer). We studied the effect of 33D1+ DC depletion or DEC-205+ DC activation in vivo using an established mouse model of allergic rhinitis (AR). Methods: Mice were injected intraperitoneally with OVA plus alum and challenged 4 times with daily intranasal administration of OVA. Immediately after the last challenge, allergic symptoms such as sneezing and nasal rubbing as well as the number of cells in the bronchoalveolar lavage fluid (BALF) and nasal lavage fluid (NALF) were counted. The levels of serum OVA-specific IgG1, IgG2a, and IgE were also determined by ELISA. Results: The allergic symptom scores were significantly decreased in 33D1+ DC-depleted or DEC-205+ DC-activated AR mice. The levels of OVA-specific IgG1, IgG2a, and IgE, and the number of NALF cells, but not BALF cells, were reduced in 33D1+ DC-depleted but not in DEC-205+ DC-activated AR mice. Moreover, the activated DEC-205+ DCs suppressed histamine release from IgE-sensitized mast cells, probably through IL-12 secretion. Conclusions: The manipulation of innate DC subsets may provide a new therapeutic strategy for controlling various allergic diseases by reducing histamine release from IgE-sensitized mast cells by driving the immune response towards Th1 dominancy via activation of DEC-205+ DCs in vivo. |
| Databáze: | OpenAIRE |
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