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

Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-κB and interferon (IFN) signalin...

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Detalles Bibliográficos
Autores principales: Xing, Yan, Wang, Xiaodan, Jameson, Stephen C., Hogquist, Kristin A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837029/
https://www.ncbi.nlm.nih.gov/pubmed/27043411
http://dx.doi.org/10.1038/ni.3419
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author Xing, Yan
Wang, Xiaodan
Jameson, Stephen C.
Hogquist, Kristin A.
author_facet Xing, Yan
Wang, Xiaodan
Jameson, Stephen C.
Hogquist, Kristin A.
author_sort Xing, Yan
collection PubMed
description Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-κB and interferon (IFN) signaling. Mice lacking the IKK kinase TAK1 underwent normal positive selection, but exhibited a specific block in functional maturation. NF-κB signaling provided protection from tumor necrosis factor (TNF) mediated death, and was required for proliferation and emigration. The interferon signature was independent of NF-κB, however IFN-αR–deficient thymocytes showed reduced STAT1 expression and phenotypic abnormality, but were competent to proliferate. Thus, both NF-κB and tonic IFN signals are involved in the final maturation of thymocytes into naïve T cells.
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spelling pubmed-48370292016-10-04 Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling Xing, Yan Wang, Xiaodan Jameson, Stephen C. Hogquist, Kristin A. Nat Immunol Article Positive selection occurs in the thymic cortex, but critical maturation events occur later in the medulla. We defined the precise stage at which T cells acquire competence to proliferate and emigrate. Transcriptome analysis of late gene changes suggested roles for NF-κB and interferon (IFN) signaling. Mice lacking the IKK kinase TAK1 underwent normal positive selection, but exhibited a specific block in functional maturation. NF-κB signaling provided protection from tumor necrosis factor (TNF) mediated death, and was required for proliferation and emigration. The interferon signature was independent of NF-κB, however IFN-αR–deficient thymocytes showed reduced STAT1 expression and phenotypic abnormality, but were competent to proliferate. Thus, both NF-κB and tonic IFN signals are involved in the final maturation of thymocytes into naïve T cells. 2016-04-04 2016-05 /pmc/articles/PMC4837029/ /pubmed/27043411 http://dx.doi.org/10.1038/ni.3419 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Xing, Yan
Wang, Xiaodan
Jameson, Stephen C.
Hogquist, Kristin A.
Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
title Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
title_full Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
title_fullStr Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
title_full_unstemmed Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
title_short Late stages of T cell maturation in the thymus involve NF-κB and tonic type I interferon signaling
title_sort late stages of t cell maturation in the thymus involve nf-κb and tonic type i interferon signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837029/
https://www.ncbi.nlm.nih.gov/pubmed/27043411
http://dx.doi.org/10.1038/ni.3419
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