DISTRIBUTION OF INTERFERON-GAMMA RECEPTORS IN NORMAL AND PSORIATIC SKIN

Recent data suggest that imbalances in production and secretion of cyt okines, in particular interferon-gamma (IFN-gamma), may be crucial in the pathogenesis of psoriasis. In order to exert its role on target ce lls, IFN-gamma has to interact with a specific cell membrane receptor termed the IFN-gamma-receptor (IFN-gamma R). We studied the distributi on of IFN-gamma Rs in frozen skin biopsies from 25 psoriatics and 5 no rmal controls with two unrelated monoclonal antibodies, and compared i ts distribution with that of the IFN-gamma-inducible HLADR- and ICAM-1 antigens. In normal skin, IFN-gamma Rs were restricted to the basal c ell layer; weak staining was found on scattered mononuclear cells in t he papillary dermis. In 13/25 active psoriatic lesions, additional sup rabasal immunoreactive foci, and in 5/25 cases, diffuse immunoreactivi ty of the entire epidermis were seen. No striking topographical simila rities between the site and number of IFN-gamma R+, HLADR+ and ICAM-1 keratinocyte foci were observed, suggesting that cytokines other than IFN-gamma induce HLADR-antigens on psoriatic keratinocytes in vivo. T he restricted distribution of lFN-gamma R on the germinative cell laye r in normal skin confirms the role played by IFN-gamma in the normal g rowth regulation of the epidermis. The de novo suprabasal expression o f IFN-gamma R in psoriasis argues against the current hypothesis that IFN-gamma R are down-regulated due to a focal excess of IFN-gamma or t ransforming growth factor alpha (TGF-alpha). Whether IFN-gamma Rs in p soriatic skin are functionally normal and involved in signal transmiss ion, remains to be studied.