Inducible T-bet deletion reveals tissue-specific requirements in NKp46+ ILC immunobiology and response to murine cytomegalovirus
Year: 2026
Type: article
Abstract: The requirement for the T-box transcription factors (TF) T-bet and Eomes in innate lymphoid cells (ILCs) beyond their development is not well understood. Here, we generate an inducible, NKp46-specific T-bet knock-out (KO) model and compare it to corresponding Eomes KO and combined T-bet Eomes double KO mice to define T-box TFs requirement in the homeostasis and function of mature NK cell and other NKp46 + ILC. Inducible T-bet deletion reduces stage IV NK cell numbers in the spleen and tissues, while preserving NK cells in the bone marrow and lymph nodes. Liver ILC1 and small intestine lamina propria NKp46 + ILC3 are also lost upon T-bet deletion, indicating the requirement for continuous T-bet expression in these ILC types. Combined T-bet and Eomes KO leads to a rapid loss of NK cells, markedly greater than with individual T-bet or Eomes KO. Direct comparison of inducible T-bet and Eomes KO models reveals that Eomes is critical for host protection against murine cytomegalovirus, whereas T-bet is dispensable, despite loss of ILC1. These findings establish the tissue-specific and non-redundant roles for T-box TFs in NKp46 + ILCs homeostasis and response to viral infection.
Source: Nature Communications
Authors: Pamela Wong, Yeeun Paik, Lily Chang, Allison Burdi, Carly Neal, Celia C. Cubitt, Jennifer Tran, Bishan Bhattarai, Lyra Morina, Nancy D. Marin, Kimberly Hwang, Hyogon Sohn, Julia A. Wagner, Jennifer A. Foltz, Wilbur M. Song, Timothy Schappe, Lynne Marsala, Mark Foster, Julia Foster, Melissa M. Berrien-Elliott, Sytse J. Piersma, Marco Colonna, Wayne M. Yokoyama, Megan A. Cooper, Todd A. Fehniger
Institution: Washington University in St. Louis
Language: English
Topic: IL-33, ST2, and ILC Pathways
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1211187675, G152912512, G1733257139, G3963282979, MICRORNA REGULATION OF NK CELL DEVELOPMENT AND FUNCTION, G775891656, G9000036566, Pre-and Postgraduate Training in Molecular Hematology, Natural Killer Cell Control of Murine Cytomegalovirus Infection, Cancer Center Support Grant, G921763661
OpenAlex ID: W7165161760
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