The transcription factor PU.1 regulates γδ T cell homeostasis

Rukhsana Jabeen, Hua Chen Chang, Ritobrata Goswami, Stephen L. Nutt, Mark Kaplan

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

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 (Sfpi1lck-/-) 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.

Original languageEnglish
Article numbere22189
JournalPLoS One
Volume6
Issue number7
DOIs
StatePublished - 2011

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T-cells
homeostasis
Homeostasis
transcription factors
T-lymphocytes
T-Lymphocytes
proto-oncogene protein Spi-1
Spleen Focus-Forming Viruses
mice
Cell Count
spleen
Proto-Oncogene Proteins c-ets
Virus Integration
Thymus
T-Lymphocyte Subsets
Transgenes
Thymus Gland
Viruses
Intestines
transgenes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

The transcription factor PU.1 regulates γδ T cell homeostasis. / Jabeen, Rukhsana; Chang, Hua Chen; Goswami, Ritobrata; Nutt, Stephen L.; Kaplan, Mark.

In: PLoS One, Vol. 6, No. 7, e22189, 2011.

Research output: Contribution to journalArticle

Jabeen, Rukhsana ; Chang, Hua Chen ; Goswami, Ritobrata ; Nutt, Stephen L. ; Kaplan, Mark. / The transcription factor PU.1 regulates γδ T cell homeostasis. In: PLoS One. 2011 ; Vol. 6, No. 7.
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