By Anna Hammerich Thysen
Chairman: Kjeld Schmiegelow
Opponent: Klaus Gottlob Müller
Opponent: Maria Jenmalm
Asthma, allergies, and autoimmune disease are common chronic diseases of the western world. The disease etiologies remains unknown, but are believed to be a combination of genetic predisposition and environmental exposure. Disease incidence has increased in recent decades and the diseases are thought to be programmed in utero supporting a role of the early environment. The aim of the present PhD thesis was to study if known risk factors are imprinted in the immune system of newborns. The hypotheses were that cesarean section and season of birth would influence the immune signature in early life. Both are known to be associated with disease. We analyzed the distribution of circulating immune cells from cord blood in the children part of the ongoing unselected COPSAC2010 birth cohort by multi-color flow cytometry. Moreover, airway mucosal
cytokines and chemokines of 1-month-old children were studied as an immunological model of a target organ for later disease development.
We found a different distribution of circulating immune cells in newborns delivered by cesarean section as compared to natural birth. Infants born by cesarean section showed elevated frequencies of BDCA-3+ dendritic cells and CD25+CD127low/-regulatory T cells, but lower frequencies of neutrophils. The divergent immune cell compartment was associated to low gestational age for children born by pre-labor cesarean section, but not for other delivery modes. The results suggest the occurrence of immune programming at birth and that delivery before full immune maturation as in the case of pre-labor cesarean section have graver effects. We found an association between season of birth and the distribution of circulating immune cells in cord blood with a general pattern of up-regulation during the winter period. This was mirrored in the signature of immune mediators in the airway epithelial lining fluid. The distribution of cord blood immune cells and airway inflammatory mediators was skewed towards Th1 and Th17 responses in winter and spring births and towards Th2 responses in newborns from fall term. We speculate that the seasonal-related
maternal exposome is reflected in the newborn immune system. These data supports the notion that environmental factors imprints immunological variation already in the perinatal life. In conclusion, studies on early immunological priming may be critical in order to understanding early
disease programming and subsequent to be able to direct future research on disease preventative strategies. We identified mode of delivery and birth season as important risk factors acting on the perinatal immune system. Collectively, our results suggest that the neonatal immune system may be imprinted in perinatal life by known risk factors for later disease development.