Striking similarity: GATA-3 regulates ILC2 and Th2 cells

Abstract

Innate lymphoid cells (ILCs) and T helper (Th) cells share similar effector functions. In this issue of Immunity, Hoyler et al. (2012) and Mjosberg et al. (2012) demonstrate that GATA-3, a Th2 regulator, controls ILC2 differentiation, maintenance, and function.

Figure 1. GATA-3 Is Essential for ILC2 Development and Function in Mice

GATA-3 determines the lineage specification of ILC2. GATA-3 is not only important for the maturation of ILC2P but also essential for the maintenance of ILC2P and mature ILC2. Bone marrow resident progenitors contain a population of cells that are Lin⁻Sca1^hiId2^hi. These cells have high expression of GATA-3 and Id2 and show similar gene profile to mature ILC2, thus representing ILC2-specific progenitors (ILC2P). After adoptive transfer, ILC2P cells migrate to the gut preferentially and differentiate into functional ILC2 with production of effector cytokines (IL-13, IL-5, and IL-4), consistent with the expression of gut homing receptor CCR9. Mature ILC2 cells in the gut do not express α4β7 but upregulate KLRG1. ILC2 cytokines stimulate gut epithelial cells to produce protective factors (e.g., angiogenin and mucin) to control helminth infection.