TCF-1 controls ILC2 and NKp46+RORγt+ innate lymphocyte differentiation and protection in intestinal inflammation.

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.

• Authors: Lisa A Mielke, Joanna R Groom, Lucille C Rankin, Cyril Seillet, Frederick Masson, Tracy Putoczki, Gabrielle T Belz
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 191 Issue 8 Pg. 4383-91 (Oct 15 2013) ISSN: 1550-6606 [Electronic] United States
• PMID: 24038093 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antigens, Ly
• GATA3 Transcription Factor
• Gata3 protein, mouse
• Hepatocyte Nuclear Factor 1-alpha
• Hnf1a protein, mouse
• Interleukin-13
• Interleukin-5
• Interleukins
• Natural Cytotoxicity Triggering Receptor 1
• Ncr1 protein, mouse
• Notch2 protein, mouse
• Nuclear Receptor Subfamily 1, Group F, Member 3
• Receptor, Notch2
• T Cell Transcription Factor 1
• T-Box Domain Proteins
• T-box transcription factor TBX21
• interleukin-22

Topics

• Animals
• Antigens, Ly (metabolism)
• Cell Differentiation (immunology)
• Citrobacter rodentium (immunology)
• Enterobacteriaceae Infections (immunology)
• GATA3 Transcription Factor (metabolism)
• Hepatocyte Nuclear Factor 1-alpha
• Inflammation (immunology, microbiology)
• Interleukin-13 (biosynthesis)
• Interleukin-5 (biosynthesis)
• Interleukins (biosynthesis)
• Intestines (immunology, microbiology)
• Killer Cells, Natural (metabolism)
• Lymphocyte Activation
• Mice
• Mice, Knockout
• Mucous Membrane (cytology, immunology)
• Natural Cytotoxicity Triggering Receptor 1 (metabolism)
• Nuclear Receptor Subfamily 1, Group F, Member 3 (metabolism)
• Receptor, Notch2 (metabolism)
• T Cell Transcription Factor 1 (genetics, metabolism)
• T-Box Domain Proteins (biosynthesis, immunology)
• T-Lymphocytes (metabolism)