title: TGF-β-mediated airway tolerance to allergens induced by peptide-based immunomodulatory mucosal vaccination.
abstract: We sought to modulate mucosal immune responses using neonatal vaccination to avert the development of allergic airways disease (AAD). Pulmonary pathology in AAD is driven by T helper (TH)2 cytokines, in particular interleukin (IL)4 and IL13, the expression and actions of which are regulated by the transcription factor STAT6. We developed a peptide homolog of STAT6, STAT6-IP. Neonatal mice given, intranasally, STAT6-IP, in an effort to modulate de novo airways immune responses, developed tolerance following subsequent allergen sensitization, with either ovalbumin or ragweed allergens, as demonstrated by reduced TH2 cytokines and specific immunoglobulin (Ig)E and the significant increases in the latency-associated peptide (LAP)(+) T-regulatory (Treg) cell subset and expression of transforming growth factor (TGF)-β. This regulatory phenotype was transferrable by CD4(+) T cells or CD11c(+) dendritic cells (DCs) derived from STAT6-IP-vaccinated mice. Anti-TGF-β treatment during allergen sensitization, however, re-established the pro-inflammatory TH2 response. Thus, neonatal STAT6-IP vaccination induces prospective TGF-β-dependent tolerance to allergen and constitutes a novel highly effective immunomodulatory allergy prevention strategy.
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: H
authors.initials: H
authors.lastname: Michael
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Xue
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: J
authors.initials: J
authors.lastname: Shan
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: B D
authors.initials: BD
authors.lastname: Mazer
authors.affiliation: Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.
authors.forename: C T
authors.initials: CT
authors.lastname: McCusker
mesh_terms: D019264:Adoptive Transfer; D000485:Allergens / Q000008:administration & dosage / Q000276:immunology; D000818:Animals; D000831:Animals, Newborn; D001249:Asthma / Q000276:immunology*; D002469:Cell Separation; D003888:Desensitization, Immunologic / Q000379:methods*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000276:immunology*; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction; D050800:STAT6 Transcription Factor / Q000008:administration & dosage / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology*; D022223:Vaccines, Subunit / Q000276:immunology
chemical_list: D000485:Allergens; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D016212:Transforming Growth Factor beta; D022223:Vaccines, Subunit