Immunoregulatory sensory circuits in group 3 innate lymphoid cell (ILC3) function and tissue homeostasis

Recent years have seen a revolution in our understanding of how cells of the
immune system are modulated and regulated not only via complex interactions
with other immune cells, but also through a range of potent inputs derived from diverse and varied biological systems. Within complex tissue environments,
such as the gastrointestinal tract and lung, these systems act to orchestrate and
temporally align immune responses, regulate cellular function, and ensure
tissue homeostasis and protective immunity. Group 3 Innate Lymphoid Cells
(ILC3s) are key sentinels of barrier tissue homeostasis and critical regulators of
host-commensal mutualism - and respond rapidly to damage, inflammation and
infection to restore tissue health. Recent findings place ILC3s as strategic
integrators of environmental signals. As a consequence, ILC3s are ideally
positioned to detect perturbations in cues derived from the environment – such
as the diet and microbiota – as well as signals produced by the host nervous,
endocrine and circadian systems. Together these cues act in concert to induce
ILC3 effector function, and form critical sensory circuits that continually function
to reinforce tissue homeostasis. In this review we will take a holistic, organismal
view of ILC3 biology and explore the tissue sensory circuits that regulate ILC3
function and align ILC3 responses with changes within the intestinal
environment.