Keratinocyte CDw60 expression is modulated by both a Th-1 type cytokine IFN-gamma and Th-2 cytokines IL-4 and IL-13: Relevance to psoriasis

Psoriasis is a chronic skin disease with an immunocytic infiltrate, includi ng activated T lymphocytes, producing multiple cytokines that can influence the phenotype of epidermal keratinocytes. In these studies we examined the effect of the cytokines interferon-gamma and interleukin-13 or interleukin -1 on keratinocytes, alone and in combination, on surface levels of HLA-DR, intercellular adhesion molecule 1, and CDw60, as well as the transcription factors STAT1, STAT6, and BCL6. As CDw60 is an acetylated form of the G(D3 ) ganglioside and may function as a T cell costimulatory molecule, the modu lation of CDw60 expression by keratinocytes in psoriatic lesions was highli ghted to gain insight into potentially important T cell-keratinocyte intera ctions. Interferon-gamma was observed to block the interleukin-4-or interle ukin-13-mediated induction of CDw60 on cultured keratinocytes, but not indu ction of the transcription factor STAT6. Interleukin-13 and interleukin-4 w ere unable to block interferon-gamma -mediated induction of STAT1 or BCL6, however, or the upregulation of intercellular adhesion molecule 1 and HLA-D R. In psoriatic plaques, CDw60 was not consistently detected on keratinocyt es in acute lesions, but was detected predominantly on basal layer keratino cytes in chronic lesions. In addition we found that BCL6 levels were increa sed in psoriatic lesions; in acute lesions BCL6 was primarily localized in the basal layer keratinocytes, whereas in chronic plaques nuclear BCL6 was predominantly expressed by keratinocytes in the suprabasal cell layers. The se studies highlight the complex modulation of the keratinocyte phenotype b y immunocyte-derived cytokines, in which induction of CDw60 involving inter leukin-4, or interleukin-13 was antagonized by interferon-gamma. We suggest in psoriatic plaques that the presence or absence of CDw60 expression by k eratinocytes may reflect the dynamic interplay between Th-1-type cytokines such as interferon-gamma and Th-2-type cytokines such as interleukin-4 and interleukin-13. The ability of interferon-gamma to induce the transcription repressor BCL6 may also contribute to the overall immunologic events in sk in, including suppression of the intermediates in the synthetic pathway lea ding to expression of the T cell costimulatory ganglioside CDw60.