Regulation of alphabeta/gammadelta T cell development by the activator protein 1 transcription factor c-Jun.
c-Jun is a member of the AP-1 family of transcription factors, the activity of which is strongly augmented by TCR signaling. To elucidate the functions of c-Jun in mouse thymic lymphopoiesis, we conditionally inactivated c-Jun specifically during early T cell development. The loss of c-Jun resulted in enhanced generation of gammadelta T cells, whereas alphabeta T cell development was partially arrested at the double-negative 3 stage. The increased generation of gammadelta T cells by loss of c-Jun was cell autonomous, because in a competitive reconstitution experiment the knockout-derived cells produced more gammadelta T cells than did the control cells. C-jun-deficient immature T cells failed to efficiently repress transcription of IL-7Ralpha, resulting in augmented IL-7Ralpha mRNA and surface levels. Chromatin immunoprecipitation assays revealed binding of c-Jun to AP-1 binding sites present in the IL-7Ralpha promoter, indicating direct transcriptional regulation. Thus, c-Jun controls the transcription of IL-7Ralpha and is a novel regulator of the alphabeta/gammadelta T cell development.
Riera-Sans
Lluís
L
London Research Institute, Cancer Research, Mammalian Genetics Laboratory, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London, UK.
Behrens
Axel
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D019426:Integrases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics / Q000502:physiology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis / Q000276:immunology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis / Q000276:immunology*; D020395:Receptors, Interleukin-7 / Q000235:genetics; D013601:T-Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology
D016755:Proto-Oncogene Proteins c-jun; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D020395:Receptors, Interleukin-7; C045073:Cre recombinase; D019426:Integrases