130: Tcf-1 controls innate lymphoid cell differentiation and protection in intestinal inflammation

Abstract

Innate lymphoid cell (ILC) populations play a central role in conferring protective immunity at the mucosal frontier. We demonstrate that Transcription factor 7 ( Tcf7 , which encodes Tcf-1), a transcription factor also important for T cell differentiation, is expressed by multiple ILC subsets including ILC2 and NKp46 + ILC3 which confer protection against lung and intestinal inflammation. Tcf-1 was intrinsically required for the differentiation of both ILC2 and NKp46 + ILC3. Loss of Tcf-1 expression impaired the capacity of inflammatory cytokine production IL-5, IL-13 and IL-22 and resulted in crippled responses to intestinal infection with Citrobacter rodentium . Furthermore, a reduction in T-bet expression required for Notch-2-dependent development of NKp46 + ILC3, showed a dose-dependent reduction in Tcf-1 expression. Collectively, our findings demonstrate an essential requirement for Tcf-1 in ILC2 differentiation and reveal a link between Tcf7 , Notch and Tbx21 in NKp46 + ILC3 development.