Estrogen receptor-beta signaling protects epidermal cytokine expression and immune function from UVB-induced impairment in mice

Abstract

A previous study in the hairless mouse, in which the photoimmune protective properties of a topical phytoestrogen or 17-β-estradiol were abrogated by the estrogen receptor antagonist ICI 182,780, revealed that estrogen receptor (Er) signaling is involved in the regulation of the suppression of immune function by UVB (290–320 nm) radiation. Here we identify the expression of Er-β but not Er-α mRNA in hairless mouse skin, whereas Er-α and Er-β mRNA were present in normal haired mouse skin. This suggests that the non-classical estrogen target Er-β is involved in the photoimmune modulation, and is consistent with Er-α being more closely associated with hair growth control, as indicated by other studies. In mice with a null mutation for Er-β, there was a significant exacerbation of the solar simulated UV (290–400 nm)-induced suppression of contact hypersensitivity. Immunohistochemical analysis revealed that the Er-β deficiency inhibited the normally immunoprotective upregulation by the UVA (320–400 nm) waveband of the epidermal expression of the cytokines IFN-γ and IL-12. Er-β deficiency also significantly increased the UVB-induced expression of the immunosuppressive cytokine IL-10. Thus Er signallingvia the Er-β is evidently a major regulator of the UVA and UVB waveband interactions that determine the skin's immune functional status, and achieves this by normalization of the cutaneous cytokine array in the UV-irradiated skin.