T Cell Factor 1 Is Required for Group 2 Innate Lymphoid Cell Generation

SummaryGroup 2 innate lymphoid cells (ILC2) are innate lymphocytes that confer protective type 2 immunity during helminth infection and are also involved in allergic airway inflammation. Here we report that ILC2 development required T cell factor 1 (TCF-1, the product of the Tcf7 gene), a transcription factor also implicated in T cell lineage specification. Tcf7−/− mice lack ILC2, and were unable to mount ILC2-mediated innate type 2 immune responses. Forced expression of TCF-1 in bone marrow progenitors partially bypassed the requirement for Notch signaling in the generation of ILC2 in vivo. TCF-1 acted through both GATA-3-dependent and GATA-3-independent pathways to promote the generation of ILC2. These results are reminiscent of the critical roles of TCF-1 in early T cell development. Hence, transcription factors that underlie early steps of T cell development are also implicated in the development of innate lymphoid cells.

► TCF-1 is required for the generation of ILC2 ► ILC2-mediated immune responses are compromised in Tcf7−/− mice ► TCF-1 promotes ILC2 development under Notch signaling ► TCF-1 acts through both GATA-3-dependent and GATA-3-independent mechanisms