T-bet concomitantly controls migration, survival, and effector functions during the development of Valpha14i NKT cells.
Valpha14i natural killer T (NKT)-cell function has been implicated in a number of disease conditions. The molecular events that drive Valpha14i NKT-cell development remain elusive. We recently showed that T-bet is required for the terminal maturation of these cells. Here we identify some of the genetic targets of T-bet during Valpha14i NKT-cell lineage development. Microarray gene-expression analyses on developing Valpha14i NKT cells were performed and provide a molecular framework to study these maturation events. In vitro ectopic expression of T-bet in immature Valpha14i NKT cells, which do not yet express T-bet, was sufficient to promote Valpha14i NKT-cell maturation, driving the expression of multiple genes, including those that participate in migration, survival, and effector functions. By regulating the expression of T-helper 1 (Th1)-associated cytokines, chemokines, chemokine receptors, and molecules involved in cytolysis, T-bet defines the unique lineage attributes of mature Valpha14i NKT cells and acts to link these attributes to a developmental process.
Matsuda
Jennifer L
JL
Integrated Department of Immunology, National Jewish Medical and Research Center, University of Colorado Health Science Center, Denver, CO, USA.
Zhang
Qianjun
Q
Ndonye
Rachel
R
Richardson
Stewart K
SK
Howell
Amy R
AR
Gapin
Laurent
L
D000818:Animals; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D020869:Gene Expression Profiling; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D012190:Retroviridae / Q000235:genetics / Q000276:immunology; D020825:T-Box Domain Proteins; D014157:Transcription Factors / Q000276:immunology*; D000098815:T-bet Transcription Factor
D011948:Receptors, Antigen, T-Cell; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D014157:Transcription Factors