T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow
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T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow. / Daussy, Cécile; Faure, Fabrice; Mayol, Katia; Viel, Sébastien; Gasteiger, Georg; Charrier, Emily; Bienvenu, Jacques; Henry, Thomas; Debien, Emilie; Hasan, Uzma A; Marvel, Jacqueline; Yoh, Keigyou; Takahashi, Satoru; Prinz, Immo; de Bernard, Simon; Buffat, Laurent; Walzer, Thierry.
In: J EXP MED, Vol. 211, No. 3, 10.03.2014, p. 563-77.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - T-bet and Eomes instruct the development of two distinct natural killer cell lineages in the liver and in the bone marrow
AU - Daussy, Cécile
AU - Faure, Fabrice
AU - Mayol, Katia
AU - Viel, Sébastien
AU - Gasteiger, Georg
AU - Charrier, Emily
AU - Bienvenu, Jacques
AU - Henry, Thomas
AU - Debien, Emilie
AU - Hasan, Uzma A
AU - Marvel, Jacqueline
AU - Yoh, Keigyou
AU - Takahashi, Satoru
AU - Prinz, Immo
AU - de Bernard, Simon
AU - Buffat, Laurent
AU - Walzer, Thierry
PY - 2014/3/10
Y1 - 2014/3/10
N2 - 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.
AB - 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.
KW - Adoptive Transfer
KW - Animals
KW - Bone Marrow/metabolism
KW - Cell Differentiation/immunology
KW - Cell Lineage/immunology
KW - DNA Primers/genetics
KW - Flow Cytometry
KW - Gene Knock-In Techniques
KW - Killer Cells, Natural/cytology
KW - Liver/metabolism
KW - Mice
KW - Microarray Analysis
KW - Models, Animal
KW - Real-Time Polymerase Chain Reaction
KW - Stem Cell Niche/immunology
KW - T-Box Domain Proteins/genetics
U2 - 10.1084/jem.20131560
DO - 10.1084/jem.20131560
M3 - SCORING: Journal article
C2 - 24516120
VL - 211
SP - 563
EP - 577
JO - J EXP MED
JF - J EXP MED
SN - 0022-1007
IS - 3
ER -