Sensing of physiological regulators by innate lymphoid cells.

Cyril Seillet,Nicolas Jacquelot

doi:10.1038/s41423-019-0217-1

Abstract

Maintenance of homeostasis and immune protection rely on the coordinated action of different physiological systems. Bidirectional communication between the immune system and physiological systems is required to sense and restore any disruption of equilibrium. Recent transcriptomic analyses of innate lymphoid cells (ILCs) from different tissues have revealed that ILCs express a large array of receptors involved in the recognition of neuropeptides, hormones and metabolic signals. ILCs rapidly secrete effector cytokines that are central in the development and activation of early immune responses, but they also constitutively secrete mediators that are important for tissue homeostasis. To achieve these functions effectively, ILCs integrate intrinsic and extrinsic signals that modulate their constitutive and induced activity. Disruption of the regulation of ILCs by physiological regulators leads to altered immune responses with harmful consequences for the organism. An understanding of these complex interactions between the immune system and physiological mediators is crucial to decipher the events leading to the protective versus pathological effects of these cells.

Highlights

SENSING OF PATHOLOGICAL AND PHYSIOLOGICAL SIGNALS Life consists of the maintenance of a dynamic equilibrium through regulation of key variables within an acceptable range
Stress is defined as a state of threatened homeostasis, and reestablishment of this homeostasis is achieved through complex interactions of the endocrine system, autonomic nervous system and immune systems.[1]
Mice without RET show increased propensity towards gut inflammation that leads to altered microbial communities.[63]. These findings demonstrate the direct influence of enteric glial cells on ILC3 functions and how glial-derived ligands facilitate the maintenance of gut homeostasis and its involvement in gut defense

Summary

INTRODUCTION

SENSING OF PATHOLOGICAL AND PHYSIOLOGICAL SIGNALS Life consists of the maintenance of a dynamic equilibrium through regulation of key variables within an acceptable range These variables include blood pH, osmolarity and glucose levels; sodium, calcium and oxygen concentrations; and body temperature. We propose that ILCs integrate physiological signals that modulate their constitutive activity in a tissue- and time-specific manner This regulation involves the specific expression of receptors that are able to sense neuropeptides, hormones and metabolic signals. ILC3s ILC3s are greatly enriched in the intestine Their capacity to produce IL-22 promotes colonization of the intestine by beneficial commensal bacteria that protect against intestinal inflammation.[27,28] Perturbed ILC3 responses are associated with impaired capacity to maintain epithelial defenses and mucosal barrier function, resulting in disastrous consequences.[29] ILC3s are divided into three subsets: (i) LTi cells, which are required for the

C Seillet and N Jacquelot

CONCLUSION

449 REFERENCES