Transplacental immune modulation with a bacterial-derived agent protects against allergic airway inflammation

  Research In-Press Preview Cell biology Immunology Free access | 10.1172/JCI12263 

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, allergic asthma alone affecting over 300 million people worldwide. Epidemiological studies demonstrate that environmental stimuli are associated with either 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 towards 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 T-regulatory 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 development of transplacental immune reprogramming approaches for primary disease prevention.

View PDF Adobe pdf file icon

(You must be logged in to add and reply comments)

Interasma on Twitter

Interasma RT @Aller_MD: “Alarm Raised on Safety of Commercial Probiotics. Few data on potential harms, for which there are grounds for concern” https…
14hreplyretweetfavorite
Interasma RT @Aller_MD: “More than three fourths of patients with longstanding hidradenitis suppurativa (HS) responded to treatment with the anti-IL-…
14hreplyretweetfavorite
Interasma RT @Aller_MD: The latest Allergy, Asthma & Immunology! https://t.co/dbY1wnP1Um Thanks to @wheezemd @EMJRespiratory @heretolearnkids #electr
14hreplyretweetfavorite
Interasma RT @Aller_MD: The latest Allergists on Social Media! https://t.co/YmLyQvzjlM Thanks to @Interasma #asthma #ers2018
14hreplyretweetfavorite
Interasma RT @Aller_MD: Rhinitis in Children and Adolescents with Asthma: Ubiquitous, Difficult to Control, and Associated with Asthma Outcomes https…
14hreplyretweetfavorite

Editor: Juan C. Ivancevich, MD

Copyright © Interasma 2003-2017  •  Terms of Use  •  Privacy Policy  •  Contact Us  •  Sitemap

Powered by FREI SA

InterAsma