Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/117681
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Type: Journal article
Title: Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation
Author: Mincham, K.T.
Scott, N.M.
Lauzon-Joset, J.-.F.
Leffler, J.
Larcombe, A.N.
Stumbles, P.A.
Robertson, S.A.
Pasquali, C.
Holt, P.G.
Strickland, D.H.
Citation: The Journal of Clinical Investigation, 2018; 128(11):4856-4869
Publisher: American Society for Clinical Investigation
Issue Date: 2018
ISSN: 0021-9738
1558-8238
Statement of
Responsibility: 
Kyle T. Mincham, Naomi M. Scott, Jean-Francois Lauzon-Joset, Jonatan Leffler, Alexander N. Larcombe, Philip A. Stumbles, Sarah A. Robertson, Christian Pasquali, Patrick G. Holt and Deborah H. Strickland
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.
Keywords: Allergy; Cell Biology; Immunology
Rights: The JCI is an open access journal. All research content is freely available immediately upon publication, and all articles published in the JCI are deposited in PubMed Central (PMC). Users are allowed to read, download, print, search, or link to the full texts of the articles under the "fair use" limitations of US copyright law.
RMID: 0030099247
DOI: 10.1172/jci122631
Grant ID: http://purl.org/au-research/grants/nhmrc/1047212
Appears in Collections:Medical Sciences publications

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