T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow Journal Article
| Authors: | Daussy, C.; Faure, F.; Mayol, K.; Viel, S.; Gasteiger, G.; Charrier, E.; Bienvenu, J.; Henry, T.; Debien, E.; Hasan, U. A.; Marvel, J.; Yoh, K.; Takahashi, S.; Prinz, I.; De Bernard, S.; Buffat, L.; Walzer, T. |
| Article Title: | T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow |
| Abstract: | Trail+DX5-Eomes- natural killer (NK) cells arise in the mouse fetal liver and persist in the adult liver. Their relationships with Trail-DX5+ NK cells remain controversial. We generated a novel Eomes-GFP reporter murine model to address this question. We found that Eomes- NK cells are not precursors of classical Eomes+ NK cells but rather constitute a distinct lineage of innate lymphoid cells. Eomes- NK cells are strictly dependent on both T-bet and IL-15, similarly to NKT cells. We observed that, in the liver, expression of T-bet in progenitors represses Eomes expression and the development of Eomes+ NK cells. Reciprocally, the bone marrow (BM) microenvironment restricts T-bet expression in developing NK cells. Ectopic expression of T-bet forces the development of Eomes- NK cells, demonstrating that repression of T-bet is essential for the development of Eomes+ NK cells. Gene profile analyses show that Eomes- NK cells share part of their transcriptional program with NKT cells, including genes involved in liver homing and NK cell receptors. Moreover, Eomes- NK cells produce a broad range of cytokines, including IL-2 and TNF in vitro and in vivo, during immune responses against vaccinia virus. Thus, mutually exclusive expression of T-bet and Eomes drives the development of different NK cell lineages with complementary functions. © 2014 Daussy et al. |
| Keywords: | controlled study; protein expression; unclassified drug; nonhuman; animal cell; mouse; interleukin 2; gene expression; gene expression profiling; cell maturation; transforming growth factor beta; granulocyte macrophage colony stimulating factor; interleukin 4; interleukin 7; animal experiment; animal model; in vivo study; in vitro study; cell lineage; cytokine; immune response; gamma interferon; messenger rna; newborn; vaccinia virus; natural killer cell; natural killer cell receptor; bone marrow cell; microenvironment; liver cell; cytokine release; t lymphocyte subpopulation; interleukin 12; interleukin 15; tumor necrosis factor; natural killer t cell; interleukin 18; lymphoid cell; interleukin 7 receptor; macrophage inflammatory protein 1alpha; male; priority journal; article; eome cytokine; t bet cytokine |
| Journal Title: | Journal of Experimental Medicine |
| Volume: | 211 |
| Issue: | 3 |
| ISSN: | 0022-1007 |
| Publisher: | Rockefeller University Press |
| Date Published: | 2014-03-10 |
| Start Page: | 563 |
| End Page: | 577 |
| Language: | English |
| DOI: | 10.1084/jem.20131560 |
| PROVIDER: | scopus |
| PMCID: | PMC3949572 |
| PUBMED: | 24516120 |
| DOI/URL: | |
| Notes: | Export Date: 1 May 2014 -- CODEN: JEMEA -- Source: Scopus |
