Childhood immune maturation and allergy development:
Epigenetic regulation by maternal immunity and microbial exposure during pregnancy
The immune system of a child may be driven towards tolerance or sensitisation to allergens. The increasing allergy prevalence in affluent countries may be caused by reduced microbial stimulation, resulting in an abnormal postnatal immune maturation and regulation. Although most studies investigating the underlying mechanisms have focussed on postnatal microbial exposure, an increasing body of evidence suggests that the maternal microbial environment during pregnancy can programme the immune development of the child. Regulation by epigenetic mechanisms, heritable changes in gene expression occurring without alterations in the DNA sequences, a kind of cellular memory, may play a major role in prenatal immune programming. Immune regulatory genes in the child may be activated or silenced through e g changed DNA methylation, affecting gene expression and disease development later in life.
To identify possible allergy preventive factors supporting tolerance development, we characterise childhood immune responses in relation to maternal immunity, epigenetic regulation and microbial exposure. The vast complexity of the gut microbiome in infancy is studied with new powerful methodology in collaboration with European and American researchers. Allergy predictive markers are evaluated. We also investigate whether atopic disease can be prevented by administration of the probiotic Lactobacillus reuteri. Our research is distinguished by a combination of careful, long-term, clinical follow-up with excellent compliance rates and advanced laboratory methods. Immune characterisation includes analysis of Th1, Th2, Th17 and T regulatory function and epigenetic regulation as well as mucosal responses.
The increasing prevalence and severity of allergic diseases in countries with market economies must be counteracted by research identifying successful preventive measures, which do not exist today. Asthma is the most common chronic disease among children, with a major impact on both the physiological and psychological well-being of young children as well as on socio-economic costs. Environmental factors in early childhood play a key role for expression of allergic disease also later in life.
The gestational environment could be very important for shaping immune responses to allergens. Efficacious preventive measures, required to combat the allergy epidemic, may be identified by determining how the immune interaction between mother and child is influenced by microbial factors. We evaluate one such preventive measure, probiotic Lactobacillus reuteri administration to the mother during pregnancy and to the child during the first year of life. Reliable allergy predictors would improve future research into preventive measures counteracting the increasing prevalence and severity of allergic diseases, justifying more radical preventive approaches in vulnerable groups.
Name: Maria Jenmalm
Position: Professor of Experimental Allergology
Phone: +46 (0)10-103 41 01
Department of Clinical and Experimental Medicine
SE-581 85 Linköping
Last updated: Tue Oct 28 14:29:12 CET 2014