Estrogen receptor α (ERα) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17β-estradiol acts through ERα to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation

K. Chad Lambert, Edward M. Curran, Barbara M. Judy, Gregg Milligan, Dennis B. Lubahn, D. Mark Estes

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

The effects of 17β-estradiol (E2) on immune function have been extensively reported. The effects are dependent on concentration and duration of exposure and potential differences in signaling between the known E2 receptors, estrogen receptors (ER) α and ERβ. Through the use of ER-deficient mice, we and others have begun to demonstrate the role of the two known receptors in modulating immune functional activities. Previous studies have shown that cells of the innate immune system have altered function (bactericidal capacity) and patterns of cytokine expression (increased proinflammatory cytokine expression) through amelioration of ERα signaling. In this study, We extend these studies to analysis of T cell differentiation and proliferation in APC-dependent and APC-independent in vitro assay systems. Our results demonstrate that ERa deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-γ production by transgenic OVA peptide-specific (OT-II) CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates. The addition of E2 in this culture system did not significantly affect the production of IFN-γ. In addition, when purified CD4+ T cells from ERα-deficieet and wild-type littermates were stimulated with anti-CD3/CD28 Ab in the absence of E2, there were no significant differences an IFN-γ or IL-4 production. However, the addition of E2 significantly increased IL-4 secretion, as well as increased GATA-3 mRNA levels from ERa-replete CD4+ T cells, while this effect was abrogated in ERα-deficient CD4+ T cells.

Original languageEnglish (US)
Pages (from-to)5716-5723
Number of pages8
JournalJournal of Immunology
Volume175
Issue number9
StatePublished - Nov 1 2005

Fingerprint

T Independent Antigens
Antigen Presentation
Interleukin-4
Estrogen Receptors
Estradiol
Macrophages
T-Lymphocytes
Cytokines
T-Cell Antigen Receptor
Dendritic Cells
Cell Differentiation
Immune System
Cell Proliferation
Messenger RNA
Peptides

ASJC Scopus subject areas

  • Immunology

Cite this

Estrogen receptor α (ERα) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17β-estradiol acts through ERα to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation. / Lambert, K. Chad; Curran, Edward M.; Judy, Barbara M.; Milligan, Gregg; Lubahn, Dennis B.; Estes, D. Mark.

In: Journal of Immunology, Vol. 175, No. 9, 01.11.2005, p. 5716-5723.

Research output: Contribution to journalArticle

@article{542a141023f748689af00c196b53a10b,
title = "Estrogen receptor α (ERα) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17β-estradiol acts through ERα to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation",
abstract = "The effects of 17β-estradiol (E2) on immune function have been extensively reported. The effects are dependent on concentration and duration of exposure and potential differences in signaling between the known E2 receptors, estrogen receptors (ER) α and ERβ. Through the use of ER-deficient mice, we and others have begun to demonstrate the role of the two known receptors in modulating immune functional activities. Previous studies have shown that cells of the innate immune system have altered function (bactericidal capacity) and patterns of cytokine expression (increased proinflammatory cytokine expression) through amelioration of ERα signaling. In this study, We extend these studies to analysis of T cell differentiation and proliferation in APC-dependent and APC-independent in vitro assay systems. Our results demonstrate that ERa deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-γ production by transgenic OVA peptide-specific (OT-II) CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates. The addition of E2 in this culture system did not significantly affect the production of IFN-γ. In addition, when purified CD4+ T cells from ERα-deficieet and wild-type littermates were stimulated with anti-CD3/CD28 Ab in the absence of E2, there were no significant differences an IFN-γ or IL-4 production. However, the addition of E2 significantly increased IL-4 secretion, as well as increased GATA-3 mRNA levels from ERa-replete CD4+ T cells, while this effect was abrogated in ERα-deficient CD4+ T cells.",
author = "Lambert, {K. Chad} and Curran, {Edward M.} and Judy, {Barbara M.} and Gregg Milligan and Lubahn, {Dennis B.} and Estes, {D. Mark}",
year = "2005",
month = "11",
day = "1",
language = "English (US)",
volume = "175",
pages = "5716--5723",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "9",

}

TY - JOUR

T1 - Estrogen receptor α (ERα) deficiency in macrophages results in increased stimulation of CD4+ T cells while 17β-estradiol acts through ERα to increase IL-4 and GATA-3 expression in CD4+ T cells independent of antigen presentation

AU - Lambert, K. Chad

AU - Curran, Edward M.

AU - Judy, Barbara M.

AU - Milligan, Gregg

AU - Lubahn, Dennis B.

AU - Estes, D. Mark

PY - 2005/11/1

Y1 - 2005/11/1

N2 - The effects of 17β-estradiol (E2) on immune function have been extensively reported. The effects are dependent on concentration and duration of exposure and potential differences in signaling between the known E2 receptors, estrogen receptors (ER) α and ERβ. Through the use of ER-deficient mice, we and others have begun to demonstrate the role of the two known receptors in modulating immune functional activities. Previous studies have shown that cells of the innate immune system have altered function (bactericidal capacity) and patterns of cytokine expression (increased proinflammatory cytokine expression) through amelioration of ERα signaling. In this study, We extend these studies to analysis of T cell differentiation and proliferation in APC-dependent and APC-independent in vitro assay systems. Our results demonstrate that ERa deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-γ production by transgenic OVA peptide-specific (OT-II) CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates. The addition of E2 in this culture system did not significantly affect the production of IFN-γ. In addition, when purified CD4+ T cells from ERα-deficieet and wild-type littermates were stimulated with anti-CD3/CD28 Ab in the absence of E2, there were no significant differences an IFN-γ or IL-4 production. However, the addition of E2 significantly increased IL-4 secretion, as well as increased GATA-3 mRNA levels from ERa-replete CD4+ T cells, while this effect was abrogated in ERα-deficient CD4+ T cells.

AB - The effects of 17β-estradiol (E2) on immune function have been extensively reported. The effects are dependent on concentration and duration of exposure and potential differences in signaling between the known E2 receptors, estrogen receptors (ER) α and ERβ. Through the use of ER-deficient mice, we and others have begun to demonstrate the role of the two known receptors in modulating immune functional activities. Previous studies have shown that cells of the innate immune system have altered function (bactericidal capacity) and patterns of cytokine expression (increased proinflammatory cytokine expression) through amelioration of ERα signaling. In this study, We extend these studies to analysis of T cell differentiation and proliferation in APC-dependent and APC-independent in vitro assay systems. Our results demonstrate that ERa deficiency in splenic macrophages, but not CD11c+ splenic dendritic cells pulsed with OVA significantly enhances proliferative responses and IFN-γ production by transgenic OVA peptide-specific (OT-II) CD4+ T cells when compared with Ag-pulsed APC from wild-type littermates. The addition of E2 in this culture system did not significantly affect the production of IFN-γ. In addition, when purified CD4+ T cells from ERα-deficieet and wild-type littermates were stimulated with anti-CD3/CD28 Ab in the absence of E2, there were no significant differences an IFN-γ or IL-4 production. However, the addition of E2 significantly increased IL-4 secretion, as well as increased GATA-3 mRNA levels from ERa-replete CD4+ T cells, while this effect was abrogated in ERα-deficient CD4+ T cells.

UR - http://www.scopus.com/inward/record.url?scp=27144459373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27144459373&partnerID=8YFLogxK

M3 - Article

C2 - 16237062

AN - SCOPUS:27144459373

VL - 175

SP - 5716

EP - 5723

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 9

ER -