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Mucosal Immunol. 2015 Nov;8(6):1248-61. doi: 10.1038/mi.2015.15. Epub 2015 Mar 18.

TGF-β-mediated airway tolerance to allergens induced by peptide-based immunomodulatory mucosal vaccination.

Author information

1
Meakins-Christie Laboratories, McGill University and the MUHCRI, Montreal, Quebec, Canada.

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.

PMID:
25783968
DOI:
10.1038/mi.2015.15
[Indexed for MEDLINE]

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