Elsevier

Cellular Immunology

Volume 214, Issue 1, 25 November 2001, Pages 12-20
Cellular Immunology

Regular Article
Natural Killer Cells Express Estrogen Receptor-α and Estrogen Receptor-β and Can Respond to Estrogen Via a Non-Estrogen Receptor-α-Mediated Pathway

https://doi.org/10.1006/cimm.2002.1886Get rights and content

Abstract

Natural killer (NK) cells play a crucial role in host defense against pathogens and immune surveillance against cancer. Given that estrogens have been reported to suppress NK cell activity, we sought to elucidate the mechanisms by which estrogen mediates this effect. We demonstrate by immunocytochemical staining with estrogen receptor-α (ERα)- and estrogen receptor-β (ERβ)-specific antibodies that both ERα and ERβ are expressed in murine NK cells. We also compared the ability of high doses of 17β-estradiol (∼800 pg/ml) to regulate NK cell activity in wild-type and estrogen receptor-α-deficient (ERαKO) mice. 17β-estradiol elicited a significant decrease in NK cell activity in both wild-type and ERαKO mice (P < 0.001). These data suggest that ERβ or possibly a novel receptor is involved in mediating estrogen action on NK cell activity and raise the potential for therapeutic modulation of NK cell activity with selective estrogen receptor modulators (SERMS).

References (61)

  • B.J. Kroesen et al.

    Direct visualisation and quantification of cellular cytotoxicity using two colour flourescence

    J. Immunol. Methods

    (1992)
  • M. van den Heuvel et al.

    An analysis of the uterine lymphocyte-derived hybridoma cell line GWM 1–2 for expression of receptors for estrogen, progesterone and interleukin 2

    J. Reprod. Immunol.

    (1996)
  • J.A. Gustafsson

    Therapeutic potential of selective estrogen receptor modulators

    Curr. Opin. Chem. Biol.

    (1998)
  • L.D. Apelgren et al.

    The effect of a selective estrogen receptor modulator on the progression of spontaneous autoimmune disease in MRL lpr/lpr mice

    Cell. Immunol.

    (1996)
  • L.L. Lanier

    The origin and functions of natural killer cells

    Clin. Immunol.

    (2000)
  • R.B. Herberman et al.

    Natural killer cells: Their roles in defenses against disease

    Science

    (1981)
  • C.A. Biron et al.

    Natural killer cells in antiviral defense: Function and regulation by innate cytokines

    Annu. Rev. Immunol.

    (1999)
  • L.L. Lanier

    NK cell receptors

    Annu. Rev. Immunol.

    (1998)
  • L.L. Lanier

    Turning on natural killer cells

    J. Exp. Med.

    (2000)
  • W.E. Seaman et al.

    β-Estradiol reduces natural killer cells in mice

    J. Immunol.

    (1978)
  • W.E. Seaman et al.

    Natural killing in estrogen-treated mice responds poorly to poly I · C despite normal stimulation of circulating interferon

    J. Immunol.

    (1979)
  • W.E. Seaman et al.

    Natural killer cells, bone, and the bone marrow: Studies in estrogen-treated mice and in congenitally osteopetrotic (mi/mi) mice

    J. Immunol.

    (1979)
  • W.E. Seaman et al.

    Effect of estrogen on natural killer cells

    Arthritis Rheum.

    (1979)
  • E. Baral et al.

    Modulation of natural killer cell-mediated cytotoxicity by tamoxifen and estradiol

    Cancer

    (1995)
  • T. Fernandes-Carlos et al.

    Modulation of natural killer cell functional activity in athymic mice by beta-carotene, oestrone and their association

    Anticancer Res.

    (1997)
  • A.S. Gauchez et al.

    Effect of oestrone on the natural killer (NK) cell activity, antioxidant status and tumour growth in athymic mice xenografted with human tumours

    Anticancer Res.

    (1996)
  • N. Hanna et al.

    Enhancement of tumor metastasis and suppression of natural killer cell activity by beta-estradiol treatment

    J. Immunol.

    (1983)
  • N. Talal

    Sex steroid hormones and systemic lupus erythematosus

    Arthritis Rheum.

    (1981)
  • S. Ansar Ahmed et al.

    Sex hormones, immune responses, and autoimmune diseases

    Am. J. Pathol.

    (1985)
  • L. Jansson et al.

    Estrogen-mediated immunosuppression in autoimmune diseases

    Inflammation Res.

    (1998)
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    This work was supported by Botanical Center Grant NIH PO1ES 10535-01.

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