Foxo1 links homing and survival of naive T cells by regulating L-selectin, CCR7 and interleukin 7 receptor.
Foxo transcription factors have a conserved role in the adaptation of cells and organisms to nutrient and growth factor availability. Here we show that Foxo1 has a crucial, nonredundant role in T cells. In naive T cells, Foxo1 controlled the expression of the adhesion molecule L-selectin, the chemokine receptor CCR7 and the transcription factor Klf2, and its deletion was sufficient to alter lymphocyte trafficking. Furthermore, Foxo1 deficiency resulted in a severe defect in interleukin 7 receptor alpha-chain (IL-7Ralpha) expression associated with its ability to bind an Il7r enhancer. Finally, growth factor withdrawal induced a Foxo1-dependent increase in Sell, Klf2 and Il7r expression. These data suggest that Foxo1 regulates the homeostasis and life span of naive T cells by sensing growth factor availability and regulating homing and survival signals.
Kerdiles
Yann M
YM
Molecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, California 92093-0377, USA.
Beisner
Daniel R
DR
Tinoco
Roberto
R
Dejean
Anne S
AS
Castrillon
Diego H
DH
DePinho
Ronald A
RA
Hedrick
Stephen M
SM
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000276:immunology; D002470:Cell Survival; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005434:Flow Cytometry; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000276:immunology; D006706:Homeostasis / Q000276:immunology; D047468:Immunoprecipitation; D019041:L-Selectin / Q000096:biosynthesis* / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000032:analysis; D054400:Receptors, CCR7 / Q000096:biosynthesis* / Q000276:immunology; D020395:Receptors, Interleukin-7 / Q000096:biosynthesis* / Q000276:immunology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism*
C515371:Ccr7 protein, mouse; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D012333:RNA, Messenger; D054400:Receptors, CCR7; D020395:Receptors, Interleukin-7; C415350:interleukin-7 receptor, alpha chain; D019041:L-Selectin