Journal article
Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation
Journal of Clinical Investigation, Vol.128(11), pp.4856-4869
2018
Abstract
Chronic allergic inflammatory diseases are a major cause of morbidity, with allergic asthma alone affecting over 300 million people worldwide. Epidemiological studies demonstrate that environmental stimuli are associated with either the promotion or prevention of disease. Major reductions in asthma prevalence are documented in European and US farming communities. Protection is associated with exposure of mothers during pregnancy to microbial breakdown products present in farm dusts and unprocessed foods and enhancement of innate immune competence in the children. We sought to develop a scientific rationale for progressing these findings toward clinical application for primary disease prevention. Treatment of pregnant mice with a defined, clinically approved immune modulator was shown to markedly reduce susceptibility of their offspring to development of the hallmark clinical features of allergic airway inflammatory disease. Mechanistically, offspring displayed enhanced dendritic cell–dependent airway mucosal immune surveillance function, which resulted in more efficient generation of mucosal-homing regulatory T cells in response to local inflammatory challenge. We provide evidence that the principal target for maternal treatment effects was the fetal dendritic cell progenitor compartment, equipping the offspring for accelerated functional maturation of the airway mucosal dendritic cell network following birth. These data provide proof of concept supporting the rationale for developing transplacental immune reprogramming approaches for primary disease prevention.
Details
- Title
- Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation
- Authors/Creators
- K.T. Mincham (Author/Creator) - The Kids Research Institute AustraliaN.M. Scott (Author/Creator) - The Kids Research Institute AustraliaJ-F Lauzon-Joset (Author/Creator) - The Kids Research Institute AustraliaJ. Leffler (Author/Creator) - The Kids Research Institute AustraliaA.N. Larcombe (Author/Creator) - Curtin UniversityP.A. Stumbles (Author/Creator) - Murdoch UniversityS.A. Robertson (Author/Creator) - The University of AdelaideC. Pasquali (Author/Creator) - OM Pharma SA, Geneva, Switzerland.P.G. Holt (Author/Creator) - The Kids Research Institute AustraliaD.H. Strickland (Author/Creator) - The Kids Research Institute Australia
- Publication Details
- Journal of Clinical Investigation, Vol.128(11), pp.4856-4869
- Publisher
- American Society for Clinical Investigation
- Identifiers
- 991005544031907891
- Copyright
- © 2018 American Society for Clinical Investigation
- Murdoch Affiliation
- School of Veterinary and Life Sciences
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- International collaboration
- Citation topics
- 2 Chemistry
- 2.1 Synthesis
- 2.1.2278 Heterocyclic Synthesis Mechanisms
- Web Of Science research areas
- Medicine, Research & Experimental
- ESI research areas
- Clinical Medicine