Innate lymphoid cells as regulators of immunity, inflammation and tissue homeostasis

Abstract

Research over the last 7 years has led to the formal identification of innate lymphoid cells (ILCs), increased the understanding of their tissue distribution and has established essential functions of ILCs in diverse physiological processes. These include resistance to pathogens, the regulation of autoimmune inflammation, tissue remodeling, cancer and metabolic homeostasis. Notably, many ILC functions appear to be regulated by mechanisms distinct from those of other innate and adaptive immune cells. In this Review, we focus on how group 2 ILC (ILC2) and group 3 ILC (ILC3) responses are regulated and how these cells interact with other immune and non-immune cells to mediate their functions. We highlight experimental evidence from mouse models and patient-based studies that have elucidated the effects of ILCs on the maintenance of tissue homeostasis and the consequences for health and disease.

Functional and phenotypic heterogeneity of group 3 innate lymphoid cells

“…The innate lymphoid cell (ILC) family has been the focus of intense investigation over recent years and ILC have emerged as key players in immune responses within multiple organs, particularly barrier surfaces such as the lung, skin and gastrointestinal tract 1, 2, 3, 4. The current nomenclature broadly divides ILC into three subgroups that are defined by their master transcription factor usage and cytokine‐producing capacity, and which closely mirror CD4 + T helper (Th) cell subsets 3.…”

“…Group 2 ILC (ILC2) respond to tissue‐derived alarmins including IL‐25 and IL‐33, are characterized by their expression of GATA‐3, produce the cytokines IL‐5, IL‐9 and IL‐13 and contribute to immune responses against multicellular pathogens (such as nematode parasites) as well as the pathogenesis of type 2 inflammatory diseases including asthma and atopic dermatitis 1, 2, 3…”

Innate‐like CD8+ T‐cells and NK cells: converging functions and phenotypes

“…Thus, NK cells have been suggested to constitute the cytotoxic arm of ILCs, the innate counterpart of CD8+ T‐cells 4, 5, 6, 7, 8…”

“…These cells lack somatically rearranged antigen receptors like T‐ and B‐cell receptors, and are able to rapidly respond to microbial products, cytokine stimulation and contact with other leukocytes 3. NK cells form a distinct lineage of the family of ILCs and are often described as the cytotoxic arm of ILCs, or the innate counterpart of CD8+ T‐cells 4, 5, 6, 7, 8…”

Les cellules lymphoïdes innées

“…En effet, chaque groupe d'ILC peut produire un ensemble de cytokines qui lui est propre. Or, l'immunité développée contre les différentes agressions dépend de la production de cytokines particulières comme l'IL-17 [18] pour les infections fongiques (par exemple à Candida albicans), ou l'IL-22 pour les infections coliques comme celles ayant pour origine Citrobacter rodentium chez la souris [23]. La plasticité des ILC pourrait donc permettre d'adapter la réponse immunitaire innée tissulaire selon le type d'infection à laquelle l'organisme est confronté.…”