Tcf-1 controls innate lymphoid cell differentiation and protection in intestinal inflammation — ASN Events

Tcf-1 controls innate lymphoid cell differentiation and protection in intestinal inflammation (#130)

Lisa A Mielke 1 , Joanna Groom 1 , Lucille C Rankin 1 , Cyril Seillet 1 , Tracy Putoczki 1 , Gabrielle T Belz 1
  1. Walter and Eliza Hall Institute, Parkville, Vic, Australia

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.