Effect of ET-2 expression of innate Lymphocyte precursors (ILCPs)

Innate Lymphoid Cells (ILCs) are tissue-resident lymphoid cells that reside mostly at barrier surfaces and participate in the initial response against pathogens. They are classified into different effector programs that parallel T helper subsets based on cytokine production and transcription factor expression. They all derive from the Common Lymphoid Precursor, but the molecular mechanisms regulating ILC subset development into effector programs is not well understood. Experiments using Id2 knockout mice have previously shown that E-protein activity inhibition is an absolute requirement for development of all ILC subsets. Here, we use a genetic approach to demonstrate that small increases in E protein activity during ILC development selectively inhibit ILC2 development. ILC1 are mostly unperturbed, and ILC3 show only a minor inhibition. This effect is first evident at the ILC2P stage and is ILC intrinsic. Therefore, our results demonstrate that modulation of E protein activity can bias cell fate decisions in developing ILCs. Overall design: ILCPs (Lin-;IL7Ra+;a4ß7+;CD90+;CD25-) expressing ET-2 (GFP+) or not (GFP-) were sorted from Rag1-cre;ET-2 mice bone marrow. Three biological replicates, each sorted from 4-5 pooled mice were processed