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Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression

Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype or...

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Autores principales: Garfin, Phillip M., Min, Dullei, Bryson, Jerrod L., Serwold, Thomas, Edris, Badreddin, Blackburn, Clare C., Richie, Ellen R., Weinberg, Kenneth I., Manley, Nancy R., Sage, Julien, Viatour, Patrick
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674705/
https://www.ncbi.nlm.nih.gov/pubmed/23669396
http://dx.doi.org/10.1084/jem.20121716
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author Garfin, Phillip M.
Min, Dullei
Bryson, Jerrod L.
Serwold, Thomas
Edris, Badreddin
Blackburn, Clare C.
Richie, Ellen R.
Weinberg, Kenneth I.
Manley, Nancy R.
Sage, Julien
Viatour, Patrick
author_facet Garfin, Phillip M.
Min, Dullei
Bryson, Jerrod L.
Serwold, Thomas
Edris, Badreddin
Blackburn, Clare C.
Richie, Ellen R.
Weinberg, Kenneth I.
Manley, Nancy R.
Sage, Julien
Viatour, Patrick
author_sort Garfin, Phillip M.
collection PubMed
description Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow–independent mechanism, identifying a novel pathway to target to increase thymic function in patients.
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spelling pubmed-36747052013-12-03 Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression Garfin, Phillip M. Min, Dullei Bryson, Jerrod L. Serwold, Thomas Edris, Badreddin Blackburn, Clare C. Richie, Ellen R. Weinberg, Kenneth I. Manley, Nancy R. Sage, Julien Viatour, Patrick J Exp Med Brief Definitive Report Thymic involution during aging is a major cause of decreased production of T cells and reduced immunity. Here we show that inactivation of Rb family genes in young mice prevents thymic involution and results in an enlarged thymus competent for increased production of naive T cells. This phenotype originates from the expansion of functional thymic epithelial cells (TECs). In RB family mutant TECs, increased activity of E2F transcription factors drives increased expression of Foxn1, a central regulator of the thymic epithelium. Increased Foxn1 expression is required for the thymic expansion observed in Rb family mutant mice. Thus, the RB family promotes thymic involution and controls T cell production via a bone marrow–independent mechanism, identifying a novel pathway to target to increase thymic function in patients. The Rockefeller University Press 2013-06-03 /pmc/articles/PMC3674705/ /pubmed/23669396 http://dx.doi.org/10.1084/jem.20121716 Text en © 2013 Garfin et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Brief Definitive Report
Garfin, Phillip M.
Min, Dullei
Bryson, Jerrod L.
Serwold, Thomas
Edris, Badreddin
Blackburn, Clare C.
Richie, Ellen R.
Weinberg, Kenneth I.
Manley, Nancy R.
Sage, Julien
Viatour, Patrick
Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression
title Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression
title_full Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression
title_fullStr Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression
title_full_unstemmed Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression
title_short Inactivation of the RB family prevents thymus involution and promotes thymic function by direct control of Foxn1 expression
title_sort inactivation of the rb family prevents thymus involution and promotes thymic function by direct control of foxn1 expression
topic Brief Definitive Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3674705/
https://www.ncbi.nlm.nih.gov/pubmed/23669396
http://dx.doi.org/10.1084/jem.20121716
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