THE TYPE-I INTERFERON SYSTEM IS LOCALLY ACTIVATED IN PSORIATIC LESIONS

The expression of mRNAs encoding interferons (IFNs) and IFN-inducible proteins has been studied in psoriatic lesions and in noninvolved skin . The specific mRNAs have been detected by in situ hybridization using antisense RNAs. Signals for the expression of IFN-gamma mRNA have bee n found exclusively in cells of psoriatic lesions, and most likely rep resent a subpopulation of infiltrating leukocytes. Weak signals of IFN -alpha mRNA have been detected throughout the hyperkeratotic epidermis , although specific signals for IFN-beta mRNA expression were not dete ctable. The expression of two IFN-alpha-inducible gene products, namel y the MxA protein and the 2'-5' oligoadenylate (2-5A) synthetase, have been studied as markers for the local activation of the IFN-alpha sys tem. Expression of MxA mRNA and protein was observed in psoriatic kera tinocytes, but not in normal appearing keratinocytes adjacent to the l esions. Similarly, 2-5A synthetase expression was markedly elevated in psoriatic keratinocytes. The results of the present study indicate th at the IFN-alpha system is selectively activated in psoriatic lesions, although it remains silent in noninvolved skin. The implications of t his finding are discussed within the boundaries of current understandi ng of the cytokine network.