title: Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling.
abstract: Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. Here we defined the precise stage at which T cells acquired competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for the transcription factor NF-κB and interferon signaling. Mice lacking the inhibitor of NF-κB (IκB) kinase (IKK) kinase TAK1 underwent normal positive selection but exhibited a specific block in functional maturation. NF-κB signaling provided protection from death mediated by the cytokine TNF and was required for proliferation and emigration. The interferon signature was independent of NF-κB; however, thymocytes deficient in the interferon-α (IFN-α) receptor IFN-αR showed reduced expression of the transcription factor STAT1 and phenotypic abnormality but were able to proliferate. Thus, both NF-κB and tonic interferon signals are involved in the final maturation of thymocytes into naive T cells.
authors.affiliation: The Center for Immunology, Department of Laboratory Medicine &Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Yan
authors.initials: Y
authors.lastname: Xing
authors.affiliation: The Center for Immunology, Department of Laboratory Medicine &Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Xiaodan
authors.initials: X
authors.lastname: Wang
authors.affiliation: The Center for Immunology, Department of Laboratory Medicine &Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
authors.affiliation: The Center for Immunology, Department of Laboratory Medicine &Pathology, University of Minnesota, Minneapolis, Minnesota, USA.
authors.forename: Kristin A
authors.initials: KA
authors.lastname: Hogquist
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D049109:Cell Proliferation / Q000235:genetics; D005434:Flow Cytometry; D020930:MAP Kinase Kinase Kinases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D053633:Receptor, Interferon alpha-beta / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050794:STAT1 Transcription Factor / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000276:immunology / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000099151:MAP Kinase Kinase Kinase 7
chemical_list: D020930:MAP Kinase Kinase Kinases; D016328:NF-kappa B; D053633:Receptor, Interferon alpha-beta; D050794:STAT1 Transcription Factor; D014409:Tumor Necrosis Factor-alpha; D000099151:MAP Kinase Kinase Kinase 7; C494080:Stat1 protein, mouse