Thomas Gensollen, PhD, Richard S. Blumberg, MD

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Presentation transcript:

Correlation between early-life regulation of the immune system by microbiota and allergy development Thomas Gensollen, PhD, Richard S. Blumberg, MD Journal of Allergy and Clinical Immunology Volume 139, Issue 4, Pages 1084-1091 (April 2017) DOI: 10.1016/j.jaci.2017.02.011 Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Evolution of microbiota from birth to adult life. Microbial diversity increases from birth to 3 years of life and stabilizes. Genetics, type of birth, diet, and environmental factors are associated with differences in intestinal microbial composition. C-section, Cesarean section. Journal of Allergy and Clinical Immunology 2017 139, 1084-1091DOI: (10.1016/j.jaci.2017.02.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Role of early-life microbiota in the regulation of iNKT cells and development of allergic disease in human subjects and mice. Cesarean section and antibiotic treatment are associated with modifications of the microbiota in early life and EoE development in later life. Whether these microbial modifications are directly related to these diseases in human subjects remains to be established. EoE development is an allergic disease that depends on iNKT cell activation. iNKT cell numbers, as well as CXCL16 and CD1d expression, are increased in patients with EoE less than 5 years of age. These increases are normalized by an elimination diet. An absence of microbiota in GF mice during early life leads to an accumulation of lung iNKT cells, increased CXCL16 expression, and increased susceptibility to asthma in later life. Conventionalization with microbiota during a specific early-life timeframe, but not thereafter, can normalize the number of iNKT cells in the lung and susceptibility to colitis and asthma. Journal of Allergy and Clinical Immunology 2017 139, 1084-1091DOI: (10.1016/j.jaci.2017.02.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Role of early-life microbiota in the regulation of Treg cells and development of allergic diseases in human subjects and mice. High microbial exposure during early life is associated with asthma protection and increased Treg cell function in fetal cord blood. In mice house dust mite (HDM) exposure during early life but not thereafter protects from asthma caused by the emergence of induced (Helios-negative) Treg cells. Treg cells have the capacity to accumulate in the skin of mice in response to colonization with a skin commensal bacterial strain specifically during early life and are required to establish tolerance to commensal-derived antigens in the adult. Journal of Allergy and Clinical Immunology 2017 139, 1084-1091DOI: (10.1016/j.jaci.2017.02.011) Copyright © 2017 American Academy of Allergy, Asthma & Immunology Terms and Conditions