Figure 2.

ILC2-specific transcription factors. GATA-3, which determines ILC2 development, maintenance and effector cytokines IL-5 and IL-13 production, is the master regulator of ILC2s. RORα, Bcl11b, ETS1, TCF1, and Gfi-1 are involved either in ILC2 development at early stages or in functional regulation of ILC2s after maturation. TCF1 regulates Gata3 expression at a very early stage to regulate ILC2 development. RORα and Bcl11b are also specifically required for the development of ILC2 cells. Mature ILC2s express IL-17RB, T1/ST2, and CD25 on their surface, and are responsive to stimulation by IL-25, IL-33, and/or IL-2. After fate commitment to ILC2 lineage, Bcl11b is also required for the maintenance of ILC2 identity, mainly through positive regulation of Gfi1 and Rora expression, and negative regulation of Ahr expression. Gfi-1 directly binds to the Il1rl1 locus to regulate IL-33 receptor expression, which mainly affects the homeostasis of ILC2s in the skin tissue. ETS1 is also required for the fitness of ILC2 cells in certain tissues, and it regulates IL-5 and IL-13 production by ILC2s