TCF-1 controls ILC2 and NKp46+RORgammat+ innate lymphocyte differentiation and protection in intestinal inflammation
- Author(s)
- Mielke, LA; Groom, JR; Rankin, LC; Seillet, C; Masson, F; Putoczki, T; Belz, GT;
- Details
- Publication Year 2013-10-15,Volume 191,Issue #8,Page 4383-91
- Journal Title
- Journal of immunology
- Publication Type
- Journal Article
- Abstract
- Innate lymphocyte populations play a central role in conferring protective immunity at the mucosal frontier. In this study, we demonstrate that T cell factor 1 (TCF-1; encoded by Tcf7), a transcription factor also important for NK and T cell differentiation, is expressed by multiple innate lymphoid cell (ILC) subsets, including GATA3(+) nuocytes (ILC2) and NKp46(+) ILCs (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 these ILC subsets to produce 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 among Tcf7, Notch, and Tbx21 in NKp46(+) ILC3 development.
- Publisher
- AMER ASSOC IMMUNOLOGISTS
- Research Division(s)
- Molecular Immunology; Inflammation
- Publisher's Version
- https://doi.org/10.4049/jimmunol.1301228
- NHMRC Grants
- NHMRC/1047903,
- Terms of Use/Rights Notice
- Copyright ©2014 by The American Association of Immunologists, Inc. All rights reserved
Creation Date: 2014-02-04 07:56:10
Last Modified: 2014-12-03 10:30:58