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The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis
BACKGROUND: T cell development results in the generation of both mature αβ and γδ T cells. While αβ T cells predominate in secondary lymphoid organs, γδ T cells are more abundant in mucosal tissues. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136513/ https://www.ncbi.nlm.nih.gov/pubmed/21779390 http://dx.doi.org/10.1371/journal.pone.0022189 |
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author | Jabeen, Rukhsana Chang, Hua-Chen Goswami, Ritobrata Nutt, Stephen L. Kaplan, Mark H. |
author_facet | Jabeen, Rukhsana Chang, Hua-Chen Goswami, Ritobrata Nutt, Stephen L. Kaplan, Mark H. |
author_sort | Jabeen, Rukhsana |
collection | PubMed |
description | BACKGROUND: T cell development results in the generation of both mature αβ and γδ T cells. While αβ T cells predominate in secondary lymphoid organs, γδ T cells are more abundant in mucosal tissues. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral integration site-1 (Sfpi1) is essential for early stages of T cell development, but is down regulated during the DN T-cell stage. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that in mice specifically lacking PU.1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpi1 (lck−/−)) there are increased numbers of γδ T cells in spleen, thymus and in the intestine when compared to wild-type mice. The increase in γδ T cell numbers in PU.1-deficient mice is consistent in γδ T cell subsets identified by TCR variable regions. PU.1-deficient γδ T cells demonstrate greater proliferation in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: The increase of γδ T cell numbers in Lck-Cre deleter strains, where deletion occurs after PU.1 expression is diminished, as well as the observation that PU.1-deficient γδ T cells have greater proliferative responses than wild type cells, suggests that PU.1 effects are not developmental but rather at the level of homeostasis. Thus, our data shows that PU.1 has a negative influence on γδ T cell expansion. |
format | Online Article Text |
id | pubmed-3136513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-31365132011-07-21 The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis Jabeen, Rukhsana Chang, Hua-Chen Goswami, Ritobrata Nutt, Stephen L. Kaplan, Mark H. PLoS One Research Article BACKGROUND: T cell development results in the generation of both mature αβ and γδ T cells. While αβ T cells predominate in secondary lymphoid organs, γδ T cells are more abundant in mucosal tissues. PU.1, an Ets family transcription factor, also identified as the spleen focus forming virus proviral integration site-1 (Sfpi1) is essential for early stages of T cell development, but is down regulated during the DN T-cell stage. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we show that in mice specifically lacking PU.1 in T cells using an lck-Cre transgene with a conditional Sfpi1 allele (Sfpi1 (lck−/−)) there are increased numbers of γδ T cells in spleen, thymus and in the intestine when compared to wild-type mice. The increase in γδ T cell numbers in PU.1-deficient mice is consistent in γδ T cell subsets identified by TCR variable regions. PU.1-deficient γδ T cells demonstrate greater proliferation in vivo and in vitro. CONCLUSIONS/SIGNIFICANCE: The increase of γδ T cell numbers in Lck-Cre deleter strains, where deletion occurs after PU.1 expression is diminished, as well as the observation that PU.1-deficient γδ T cells have greater proliferative responses than wild type cells, suggests that PU.1 effects are not developmental but rather at the level of homeostasis. Thus, our data shows that PU.1 has a negative influence on γδ T cell expansion. Public Library of Science 2011-07-14 /pmc/articles/PMC3136513/ /pubmed/21779390 http://dx.doi.org/10.1371/journal.pone.0022189 Text en Jabeen et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Jabeen, Rukhsana Chang, Hua-Chen Goswami, Ritobrata Nutt, Stephen L. Kaplan, Mark H. The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis |
title | The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis |
title_full | The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis |
title_fullStr | The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis |
title_full_unstemmed | The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis |
title_short | The Transcription Factor PU.1 Regulates γδ T Cell Homeostasis |
title_sort | transcription factor pu.1 regulates γδ t cell homeostasis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136513/ https://www.ncbi.nlm.nih.gov/pubmed/21779390 http://dx.doi.org/10.1371/journal.pone.0022189 |
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