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Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
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Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
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Journal Article
Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
2016
Overview
Positively selected thymocytes require a maturation phase before emigrating from the thymus. Hogquist and colleagues show that functional maturation is driven by tonic signals provided by type I interferons and the transcription factor NF-κB.
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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ 45/61
/ 631/250
/ 64/60
/ Animals
/ Cell Differentiation - genetics
/ Cell Differentiation - immunology
/ Cell Proliferation - genetics
/ Cellular signal transduction
/ MAP Kinase Kinase Kinases - genetics
/ MAP Kinase Kinase Kinases - immunology
/ MAP Kinase Kinase Kinases - 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 cells
/ Tumor Necrosis Factor-alpha - genetics
