Development and function of group 2 innate lymphoid cells

Abstract

The innate lymphoid cell (ILC) family has recently expanded with the discovery of type-2 innate lymphoid cells (ILC2). These cells arise from lymphoid progenitors in the bone marrow and, under the control of the transcriptional regulators RORα and Gata3, they mature to give rise to IL-5, IL-9 and IL-13 producing ILC2. These cells are critical components of the innate immune response to parasitic worm infections and have also been implicated in the pathogenesis of asthma and allergy. Recent advances in our understanding of the molecular regulation of ILC2 development and function now present the opportunity to develop new genetic models to assess ILC2 immune function and to investigate possible therapeutic interventions.

Figure 1

ILC2 as instigators of type-2 immunity. ILC2 play critical roles in immune responses towards helminthic parasites, viruses and allergens. In response to cytokines such as IL-25, IL-33 and TSLP, which serve as ‘distress’ signals from the epithelium, ILC produce type-2 cytokines to activate type-2 effector pathways.

Figure 2

Transcriptional control of ILC2 ontogeny. ILC2 development, similar to that of other ILC family members, requires the transcriptional regulator Id2 and potentially Notch receptor signalling. Subsequent differentiation from a committed ILC progenitor (proILC) is governed by the expression of ILC lineage-specific transcription factors. ILC2 development, via an ILC2 precursor (preILC2), is directed by the transcription factors RORα and Gata3. The specific roles of these transcription factors throughout ILC2 ontogeny in the bone marrow and peripheral tissues, and in the generation of activated cytokine-producing cells, are yet to be fully elucidated.