Type-2 innate lymphoid cells in asthma and allergy

Abstract

Type-2 innate lymphoid cells (ILC2) belong to an expanding family of innate lymphocytes that provide a potent source of immune effector cytokines at the initiation of immune responses. ILC2 arise, under the control of the transcription factors RORα and GATA3, from lymphoid progenitors in the bone marrow, to secrete type-2 cytokines including IL-5 and IL-13. Using experimental models, ILC2 have been implicated in allergic diseases, such as asthma and atopic dermatitis, but also in metabolic homeostasis. Furthermore, recent reports have indicated that ILC2 not only play roles at the initiation of type-2 immunity but can also contribute to chronic pathology, such as fibrosis, and can impact on the priming of the adaptive T-cell response. The identification of ILC2 in patients with allergic dermatitis and allergic rhinitis indicates that these cells may represent new therapeutic targets.

Keywords: cytokines; innate immunity; type-2 immunity; type-2 innate lymphoid cells.

Figures

Figure 1.

Transcriptional control of type-2 innate lymphoid cells (ILC2) development. Although the precise roles of specific transcription factors in ILC2 ontogeny are still to be elucidated, a general map is emerging in which a common lymphoid progenitor progressively commits to an ILC precursor. The data in this scheme are mainly derived from the mouse system. Subsequent activation of transcription factors such as RORγ (ILC3) and RORα (ILC2) restricts the lineages still further. GATA3 = GATA-binding protein 3; ICOS = inducible T cell costimulator; Id2 = inhibitor of DNA binding 2; KLRG1 = killer cell lectin-like receptor G1; NK = natural killer; PLZF = promyelocytic leukaemia zinc finger protein; TCF1 = T cell factor 1; TSLP = thymic stromal lymphopoietin.

Figure 2.

Type-2 innate lymphoid cells (ILC2) contribute to diverse type-2 immune responses. Stimuli such as allergens or parasitic worms lead to the release of ILC2-inducing factors such as IL-25, IL-33, and TSLP from the epithelium. These cytokines cause ILC2 to proliferate and produce type-2 cytokines and type-2 effector pathways.