The mammalian gastrointestinal tract accommodates trillions
of bacteria, many of which provide beneficial effects
to the host, including protection from pathogenic microorganisms
and essential metabolites. However, the intestinal
immune system needs to adapt to the constantly fluctuating
microbial environment at mucosal surfaces in order to maintain
homeostasis. In particular, the gut microbiota induces
the differentiation of effector Th17 cells and regulatory T cells
(Tregs) that express RORγt, the master regulator of antimicrobial
type 3 immunity. RORγt+ Tregs constitute a major
population of colonic Tregs that is distinct from thymusderived
Tregs and require bacterial antigens for differentiation.
The balance between Th17 cells and RORγt+ Tregs, that
is, the tone of the local type 3 immune response, is regulated
by the vitamin A metabolite retinoic acid produced by the
host. Furthermore, Th17 cells and RORγt+ Tregs regulate
intestinal type 2 immune responses, explaining how bacteria
block allergic reactions. Here, we review the cellular
and molecular mechanisms involved in the differentiation,
regulation and function of RORγt+ (type 3) Tregs, and discuss
the multiple equilibria that exist between effector T cells
and Tregs, as well as between different types of immune responses,
which are necessary to maintain homeostasis and
health.
Citations
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