GATA-3 promotes maturation, IFN-gamma production, and liver-specific homing of NK cells.
The GATA-3 transcription factor has a determinant role in T cell specification and is an essential mediator of T helper 2-type polarized immune responses. While both committed NK precursors and mature NK cells express GATA-3, a role of this transcription factor in murine NK cell differentiation is not known. We found that NK cells, in contrast to T cells, can be generated in the absence of GATA-3. However, while GATA-3 antagonizes IFN-gamma production in differentiating T cells, GATA-3-deficient NK cells paradoxically produced less IFN-gamma compared to control NK cells and failed to provide early protection in vivo against infection with Listeria monocytogenes. Surprisingly, GATA-3 was essential for NK cell homing to the liver. Our results suggest that GATA-3 promotes NK cell maturation and acts in this lineage to specify distinct effector phenotypes.
Samson
Sandrine I
SI
Unité des Cytokines et Développement Lymphoïde, Inserm Equipe 101, Institut Pasteur, 75724 Paris, France.
Richard
Odile
O
Tavian
Manuela
M
Ranson
Thomas
T
Vosshenrich
Christian A J
CA
Colucci
Francesco
F
Buer
Jan
J
Grosveld
Frank
F
Godin
Isabelle
I
Di Santo
James P
JP
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002678:Chimera; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D050990:GATA3 Transcription Factor; D007371:Interferon-gamma / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology; D008099:Liver / Q000378:metabolism; D051379:Mice; D015534:Trans-Activators / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494748:Gata3 protein, mouse; D015534:Trans-Activators; D007371:Interferon-gamma