Cargando…
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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |
_version_ | 1782272408962465792 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3674705 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT garfinphillipm inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT mindullei inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT brysonjerrodl inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT serwoldthomas inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT edrisbadreddin inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT blackburnclarec inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT richieellenr inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT weinbergkennethi inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT manleynancyr inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT sagejulien inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression AT viatourpatrick inactivationoftherbfamilypreventsthymusinvolutionandpromotesthymicfunctionbydirectcontroloffoxn1expression |