title: Effects of Dendritic Cell Subset Manipulation on Airway Allergy in a Mouse Model.
abstract: 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.
authors: Departments of Microbiology and Immunology, Nippon Medical School, Tokyo, Japan.
authors: Ryosuke
authors: R
authors: Murakami
authors: Yohko
authors: Y
authors: Nakagawa
authors: Masumi
authors: M
authors: Shimizu
authors: Ayako
authors: A
authors: Wakabayashi
authors: Yasuyuki
authors: Y
authors: Negishi
authors: Takachika
authors: T
authors: Hiroi
authors: Kimihiro
authors: K
authors: Okubo
authors: Hidemi
authors: H
authors: Takahashi
mesh_terms: D000534:Alum Compounds; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D019070:Cell Lineage / Q000276:immunology*; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D005699:Galactosylceramides / Q000008:administration & dosage*; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood / Q000494:pharmacology; D007074:Immunoglobulin G / Q000097:blood; D007274:Injections, Intraperitoneal; D008407:Mast Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D061251:Primary Cell Culture; D065631:Rhinitis, Allergic / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology / Q000628:therapy; D012720:Severity of Illness Index; D012912:Sneezing; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D000534:Alum Compounds; D005699:Galactosylceramides; D007074:Immunoglobulin G; C493154:alpha-galactosylceramide; C446402:ovalbumin-alum; D007073:Immunoglobulin E; D010047:Ovalbumin