Sustained E protein activity selectively inhibits ILC2 development

Abstract

Abstract Innate lymphoid cells (ILCs) are among the first cells to respond to invading pathogens. They coordinate the immune response through the use of effector programs, primed cell responses that cause release of specific cytokines. There are three ILC subsets, ILC1s, ILC2s, ILC3s. All three share a developmental requirement for Id2, a dominant negative inhibitor of the E protein family of transcription factors. To examine how E protein activity affects ILC subset development, we expressed ET-2 during ILC development in mice. ET-2 is a chimeric molecule which restores some E protein activity by competing with Id2 for E protein binding. We examined ILCs in their site of development, the bone marrow, and in a site of mature cells, the lungs. While we did not see changes in overall populations of ILC subsets between control and ET-2 mice, we did see a selective decrease in the percentage of ET-2-expressing ILC2s in ET-2 mice in both bone marrow and lungs. However, these ET-2-expressing ILC2s were still capable of secreting their effector program cytokines of IL-5 and IL-13. These results indicate that partially sustaining E protein activity negatively affects ILC2 development, but not that of ILC1s or ILC3s.