Research Group Immune regulation & Environmental factors
Within our prospective Mother-Child study LINA (Lifestyle and environmental factors & their influence of the newborn-allergy-risk Website LINA Study) we investigate the relationship between environmental exposure and allergy-relevant parameters like Th1/Th2 cytokines, inflammatory markers, regulatory T cells, MAIT cells and IgE. The main aim is to identify early markers for the development of allergic diseases providing the basis for the implementation of scientific results into strategies for disease prevention. Furthermore, the data are validated in in vitro experiments.
MAIT - Mucosal-associated invariant T cells
Recently a new group of specialized immune cells has been discovered: the mucosal-associated invariant T cells (MAIT). In humans, these cells constitute a significant population of T cells accounting to between 1% and 10% of T cells in peripheral blood and are also abundant in mucosal tissues like gut and lung. Recent studies suggest that MAIT cells contribute to chronic inflammation like inflammatory bowel disease, psoriasis, multiple sclerosis and also asthma. Due to their specialized T cell receptor MAIT cells recognize metabolites of the bacterial Vitamin B pathway. It is assumable that any alteration in bacterial metabolism will alter the activation of these cells leading to adverse health effects. The aim of this Exposome project is to investigate the response of MAIT cells to bacterial metabolite diversity and concentration modulated by environmental contaminants (e.g. pesticides). Furthermore, MAIT cells as well as environmental contaminants are measured in our prospective birth cohort studies (LINA, LISA), thereby giving the opportunity to analyze the impact on health effects.
Regulatory T cells (Treg)
Regulatory T cells (Treg) are important for controlling immune responses and thereby the development of allergic diseases. Within the LINA study (Lifestyle and environmental factors & their influence of the newborn-allergy-risk) regulatory T cells were analysed in blood samples of mother and child at various time points (34th week of pregnancy, birth, 1th and 2nd year of life). So far results show that a low number of Treg in the maternal blood during pregnancy correlates with elevated IgE levels in the cord blood, the basis for later allergic diseases (Hinz et al, 2010, Clin Exp Allergy Abstract). Furthermore, we could show that maternal smoking and environmental tobacco smoke exposure during pregnancy were associated with lower numbers of Treg in children. These children had a higher risk to develop atopic dermatitis (Hinz et al, 2012, Allergy Abstract). Follow-up investigations showed that the microRNA-223 was associated with tobacco smoke exposure during pregnancy as well as with lower numbers of Treg in children and mothers and may represent a link between environmental exposure and immune regulation (Herberth et al., 2014, JACI Abstract).
Furthermore, we were able to show that early exposure to chemicals like phthalates impacts immune regulation in newborns. Children of mothers with high concentrations of phthalate metabolites during pregnancy had lower numbers of Treg at birth and in the first years of life. These children also had a higher risk to develop atopic dermatitis and a sensitization to food allergens (Herberth et al., 2017, JACI Abstract).
Inflammatory immune response and Metabolom
New research data provide evidence that endogenous metabolites have an immunomodulatory capacity. First results in the LINA study showed that high sugar concentrations in the blood samples of newborns and infants led to the activation of a molecular complex, the inflammasome, inducing an inflammatory immune response. Furthermore, these children had an increased risk to develop respiratory disease like bronchitis. Conversely, amino acids and lyso-phosphatidylcholine (LysoPC) did inhibit the activation of the inflammasome complex (Herberth et al, 2015, JACI Abstract). Thus, the balance between endogenous metabolites seems to be important for the regulation of an inflammatory immune response independently of invading pathogens. Which environmental contaminants may disturb this balance will be investigated in future studies.