Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling

Nat Immunol. 2016 May;17(5):565-73. doi: 10.1038/ni.3419. Epub 2016 Apr 4.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Cell Proliferation / genetics
  • Flow Cytometry
  • MAP Kinase Kinase Kinases / genetics
  • MAP Kinase Kinase Kinases / immunology
  • MAP Kinase Kinase Kinases / metabolism
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • NF-kappa B / genetics
  • NF-kappa B / immunology*
  • NF-kappa B / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Receptor, Interferon alpha-beta / immunology*
  • Receptor, Interferon alpha-beta / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / immunology
  • STAT1 Transcription Factor / metabolism
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Thymocytes / immunology
  • Thymocytes / metabolism
  • Thymus Gland / cytology
  • Thymus Gland / immunology*
  • Thymus Gland / metabolism
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / immunology
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • NF-kappa B
  • STAT1 Transcription Factor
  • Stat1 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Receptor, Interferon alpha-beta
  • MAP Kinase Kinase Kinases
  • MAP kinase kinase kinase 7

Associated data

  • GEO/GSE74078