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Review
. 2016 Apr 29;352(6285):539-44.
doi: 10.1126/science.aad9378.

V体育平台登录 - How colonization by microbiota in early life shapes the immune system

Thomas Gensollen  1 , Shankar S Iyer  1 , Dennis L Kasper  2 , Richard S Blumberg  3
Affiliations
Review

V体育官网入口 - How colonization by microbiota in early life shapes the immune system

Thomas Gensollen et al. Science. .

Abstract

Microbial colonization of mucosal tissues during infancy plays an instrumental role in the development and education of the host mammalian immune system VSports手机版. These early-life events can have long-standing consequences: facilitating tolerance to environmental exposures or contributing to the development of disease in later life, including inflammatory bowel disease, allergy, and asthma. Recent studies have begun to define a critical period during early development in which disruption of optimal host-commensal interactions can lead to persistent and in some cases irreversible defects in the development and training of specific immune subsets. Here, we discuss the role of early-life education of the immune system during this "window of opportunity," when microbial colonization has a potentially critical impact on human health and disease. .

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Figures (VSports注册入口)

Fig. 1
Fig. 1. iNKT cell colonization is regulated by the microbiota during early life and influences susceptibility to colitis and asthma later in life
(A) iNKT cells migrate from the thymus to the colon during the first weeks of life. Their abnormal accumulation in the colon of GF mice leads to later-life susceptibility to oxazolone-induced colitis. Conventionalization with a standard microbiota or monocolonization with B. fragilis (B. frag) but not B. fragilis deficient in sphingolipids (B. fragΔSPT) during the window of opportunity restores colonic iNKT cell numbers and abrogates the increased susceptibility to colitis. In contrast to conventionalization with a standard microbiota during the first 2 weeks of life that decrease iNKTcell number in a mechanism dependent on CXCL16, monocolonization with B. fragilis regulates colonic iNKT cell number in a CXCL16-independent manner that depends on inhibitory sphingolipids from B. fragilis that impede iNKT cell proliferation. (B) iNKT cell accumulation in lungs of GF mice lead to later-life susceptibility to asthma. Conventionalization with a standard microbiota but not monocolonization with B. fragilis during the window of opportunity restores colonic iNKT cell numbers in a CXCL16-dependent manner and abrogates the increased susceptibility to asthma.
Fig. 2
Fig. 2. Exposure to a microbiota during early life regulates IgE levels in serum of adult mice and their sensitivity to orally induced anaphylaxis
IgE accumulates in the serum of GF mice 4 weeks after birth because of an isotype switch to IgE in mucosal B cells. “Hyper-IgE levels” lead to an exaggerated sensitivity to orally induced anaphylaxis that can be resolved through conventionalization with a standard microbiota during early life but not thereafter. Colonization of GF mice with low-diversity microbiota during the window of opportunity fails to normalize hyper-IgE levels in adult life.
Fig. 3
Fig. 3. Treg cells colonize the skin of neonatal mice and induce tolerance to commensal bacteria
Colonization of neonatal skin with a commensal microbiota leads to an accumulation of “activated” Treg cells (red cells) that specifically recognize an artificially marked antigen, with consequent tolerance to this same antigen in later life. Colonization of adult animals with the same microbiota containing the marked commensal microbiota (red triangle) does not lead to Treg cell accumulation in the skin or establish immune tolerance.
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