Differential Expression of the Transcription Factor GATA3 Specifies Lineage and Functions of Innate Lymphoid Cells

Lymphoid tissue inducer (LTi) cells are regarded as a subset of innate lymphoid cells (ILCs). However, these cells are not derived from the ILC common progenitor, which generates other ILC subsets and is defined by the expression of the transcription factor PLZF. Here we examined transcription factor(s) determining the fate of LTi progenitor versus non-LTi ILC progenitor. Conditional deletion of Gata3 resulted in the loss of PLZF+ non-LTi progenitors but not the LTi progenitors that expressed the transcription factor ROR?t. Consistently, PLZF+ non-LTi progenitors expressed high amounts of GATA3 whereas GATA3 expression was low in ROR?t+ LTi progenitors. The generation of both progenitors required the transcriptional regulator Id2, which defines the common helper-like innate lymphoid progenitor, but not cytokine signaling. Nevertheless, low GATA3 expression was necessary for the generation of functionally mature LTi cells. Thus, differential expression of GATA3 determines the fates and functions of distinct ILC progenitors. Overall design: To identify transcriptome changes from common lymphoid progenitor (CLP) to common helper-like innate lymphoid progenitor (ChILP) with RNA-Seq; To identify unique genes expressed by PD-1+ non-LTi ILC progenitor and CCR6+ LTi progenitor with RNA-Seq.