Early life imprinting of intestinal immune tolerance and tissue homeostasis

Abstract

SummaryBesides its canonical role in protecting the host from pathogens, the immune system plays an arguably equally important role in maintaining tissue homeostasis. Within barrier tissues that interface with the external microenvironment, induction of immune tolerance to innocuous antigens, such as commensal, dietary, and environmental antigens, is key to establishing immune homeostasis. The early postnatal period represents a critical window of opportunity in which parallel development of the tissue, immune cells, and microbiota allows for reciprocal regulation that shapes the long‐term immunological tone of the tissue and subsequent risk of immune‐mediated diseases. During early infancy, the immune system appears to sacrifice pro‐inflammatory functions, prioritizing the establishment of tissue tolerance. In this review, we discuss mechanisms underlying early life windows for intestinal tolerance with a focus on newly identified RORγt+ antigen‐presenting cells–Thetis cells–and highlight the role of the intestinal microenvironment in shaping intestinal immune system development and tolerance.

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring

“…The microbiome can also have a wide range of effects on shaping and training the host immune system [ 144 , 145 , 146 ]. Normal colonization of microbiota has been shown to assist in the proper development of CD8 + T cell immunity through the priming of monocytes and macrophages, which release TNF that signals conventional DCs to produce the CD8 + T cell target IL-12p40 [ 147 ].…”