Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1)

Magdalena J. Polanczyk, Corwyn Hopke, Arthur Vandenbark, Halina Offner

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110 Citations (Scopus)

Abstract

Estrogen [17-β-estradiol (E2)] is a potent driver of the FoxP3+ regulatory T cell (Treg) compartment. Recently, Tregs were further characterized by intracellular expression of the negative co-stimulatory molecule, programmed death-1 (PD-1). To clarify the role of PD-1 versus FoxP3 in E2-enhanced Treg suppression, we evaluated both markers and functional suppression in wild-type, estrogen receptor knockout (ERKO) mice and PD-1 KO mice. We demonstrate that intracellular PD-1 expression is also E2 sensitive, since E2 treatment increased intracellular PD-1 levels in CD4+ FoxP3+ cells, and PD-1 expression and Treg suppression were reduced in ERKO mice. Surprisingly, PD-1 KO mice retained normal levels of FoxP3 expression, but Tregs from these mice lacked functional suppression. However, E2 pre-treatment of PD-1 KO mice partially restored functional Treg suppression without enhancing FoxP3 expression. Thus, functional Treg suppression in immunized mice without E2 pre-treatment was more closely linked to PD-1 expression than to FoxP3 expression. However, although enhanced PD-1 expression was E2 dependent, functional suppression was still enhanced by E2 pre-treatment in the absence of PD-1. These data clearly demonstrate that E2 can affect multiple regulatory elements that influence Treg suppression, including both PD-1-dependent and PD-1-independent pathways.

Original languageEnglish (US)
Pages (from-to)337-343
Number of pages7
JournalInternational Immunology
Volume19
Issue number3
DOIs
StatePublished - Mar 2007

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Estrogens
Knockout Mice
Estrogen Receptors
Regulatory T-Lymphocytes
Estradiol
Cell Death

ASJC Scopus subject areas

  • Immunology

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Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1). / Polanczyk, Magdalena J.; Hopke, Corwyn; Vandenbark, Arthur; Offner, Halina.

In: International Immunology, Vol. 19, No. 3, 03.2007, p. 337-343.

Research output: Contribution to journalArticle

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