title: Recombinant DNA immunotherapy ameliorate established airway allergy in a IL-10 dependent pathway.
abstract: BACKGROUND
  Previous studies have established that mycobacterial infections ameliorate allergic inflammation. However, a non-infectious approach that controls allergic responses might represent a safer and more promising strategy. The 60-65 kDa heat shock protein (Hsp) family is endowed with anti-inflammatory properties, but it is still unclear whether and how single mycobacterial Hsp control allergic disorders.
  
  
  OBJECTIVE
  Therefore, in this study we determined whether the administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid could attenuate a previously established allergic response.
  
  
  METHODS
  We used an experimental model of airway allergic inflammation to test the effects of immunotherapy with DNA encoding Hsp65. Allergic mice, previously sensitized and challenged with ovalbumin, were treated with tree intramuscular doses of recombinant DNA encoding Hsp65. After treatment, mice received a second allergen challenge and the allergic response was measured.
  
  
  RESULTS
  We found that immunotherapy attenuated eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production. Moreover, we showed that the inhibition of allergic response is dependent on IL-10 production. Both Hsp65 and allergen-specific IL-10-producing cells contributed to this effect. Cells transferred from DNA-immunized mice to allergic mice migrated to allergic sites and down-modulated the Th2 response.
  
  
  CONCLUSIONS
  Our findings clearly show that immunotherapy with DNA encoding Hsp65 can attenuate an established Th2 allergic inflammation through an IL-10-dependent mechanism; moreover, the migration of allergen- and Hsp65-specific cells to the allergic sites exerts a fundamental role. This work represents a novel contribution to the understanding of immune regulation by Hsp65 in allergic diseases.
authors.affiliation: Department of Biochemistry and Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, Riberão Preto, Brazil.
authors.forename: D M
authors.initials: DM
authors.lastname: Fonseca
authors.forename: P F
authors.initials: PF
authors.lastname: Wowk
authors.forename: M O
authors.initials: MO
authors.lastname: Paula
authors.forename: L W
authors.initials: LW
authors.lastname: Campos
authors.forename: A F
authors.initials: AF
authors.lastname: Gembre
authors.forename: W M
authors.initials: WM
authors.lastname: Turato
authors.forename: S G
authors.initials: SG
authors.lastname: Ramos
authors.forename: M
authors.initials: M
authors.lastname: Dias-Baruffi
authors.forename: R
authors.initials: R
authors.lastname: Barboza
authors.forename: E
authors.initials: E
authors.lastname: Gomes
authors.forename: C L
authors.initials: CL
authors.lastname: Silva
authors.forename: M
authors.initials: M
authors.lastname: Russo
authors.forename: V L D
authors.initials: VL
authors.lastname: Bonato
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology; D018834:Chaperonin 60 / Q000235:genetics / Q000276:immunology; D004274:DNA, Recombinant / Q000008:administration & dosage* / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009166:Mycobacterium leprae / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000628:therapy*; D016896:Treatment Outcome
chemical_list: D001426:Bacterial Proteins; D018834:Chaperonin 60; D004274:DNA, Recombinant; C074119:heat-shock protein 65, Mycobacterium; D016753:Interleukin-10; D049452:Green Fluorescent Proteins