Harald Renz, MD, Patrick G. Holt, FAA, Michael Inouye, PhD, Alan C

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Presentation transcript:

An exposome perspective: Early-life events and immune development in a changing world Harald Renz, MD, Patrick G. Holt, FAA, Michael Inouye, PhD, Alan C. Logan, BA, Susan L. Prescott, MD, PhD, FRACP, Peter D. Sly, MD Journal of Allergy and Clinical Immunology Volume 140, Issue 1, Pages 24-40 (July 2017) DOI: 10.1016/j.jaci.2017.05.015 Copyright © 2017 Terms and Conditions

Fig 1 The metaexposome is defined as the total environmental exposures affecting all living systems and their genomes. This occurs in a bidirectional manner within the ecological theatre in which all life resides. From an anthropocentric viewpoint, this includes the policies and practices that illuminate the theatre. As well as addressing the adverse exposures eroding health, we need to promote exposures or resiliency, which extend from biological influences to psychological assets and value systems. (Image: Susan Prescott) Journal of Allergy and Clinical Immunology 2017 140, 24-40DOI: (10.1016/j.jaci.2017.05.015) Copyright © 2017 Terms and Conditions

Fig 2 Immune function maturation kinetics. Maturation of key aspects of innate and adaptive immune function is incomplete at birth, resulting in increased susceptibility to a variety of diseases, including infections and allergic sensitization. The degree of impairment of immune competence during early life is highly variable; however, children with an atopic family history cluster toward the “slow development” end of the population spectrum, displaying reduced functionality at birth and taking longer to attain adult-equivalent levels of immune competence. Journal of Allergy and Clinical Immunology 2017 140, 24-40DOI: (10.1016/j.jaci.2017.05.015) Copyright © 2017 Terms and Conditions

Fig 3 The microbial exposome. Environmental microbes come from different sources, and the composition differs according to lifestyle and living conditions. Also, dietary components (eg, vegetables and fruits) harbor microbes, which are ingested. Additional sources are microbes from pets and vertebrates (eg, rodents) and nonvertebrates (eg, mites and cockroaches), which are also associated with certain pure living conditions. Mucosal contact sites are associated with ingestion and inhalation (together with absorption through the skin). Timing also plays an important role. A particular window of contact is the prenatal and early postnatal period, and mode of delivery is important. In terms of immunologic consequences, microbes trigger through pattern recognition receptors (PRRs) and activation of innate and adaptive immune responses. Epigenetic regulation plays an important role, leading to modulation of T-cell effector responses and generation of immunologic tolerance. Journal of Allergy and Clinical Immunology 2017 140, 24-40DOI: (10.1016/j.jaci.2017.05.015) Copyright © 2017 Terms and Conditions

Fig 4 Lifestyle factors can contribute to or diminish microbial diversity. Many aspects of modernity promote dysbiosis. Some of the consequences include intestinal permeability and resultant low-grade inflammation, with multisystem effects, including emotional and metabolic disturbances. In turn, this might contribute to a continuing cycle of dysbiosis. Journal of Allergy and Clinical Immunology 2017 140, 24-40DOI: (10.1016/j.jaci.2017.05.015) Copyright © 2017 Terms and Conditions

Fig 5 Schematic representation of the complexity between exposure to plasticizers and potential health effects. Solid blue lines represent known adverse health outcomes, and dotted red lines indicate postulated adverse health outcomes. BDNF, Brain-derived neurotrophic factor; ER, estrogen receptors; IUGR, intrauterine growth restriction. Journal of Allergy and Clinical Immunology 2017 140, 24-40DOI: (10.1016/j.jaci.2017.05.015) Copyright © 2017 Terms and Conditions

Fig 6 Big data and bioinformatics to study the exposome. Against a genomic background, environmental exposures affect molecular and microbial systems, variation of which can be measured by using -omics technologies and statistical modeling with the help of high-performance computing to address clinical and biological questions. Journal of Allergy and Clinical Immunology 2017 140, 24-40DOI: (10.1016/j.jaci.2017.05.015) Copyright © 2017 Terms and Conditions