Cutaneous lymphocyte localization in the pathogenesis of psoriasis.

Abstract

Psoriasis is one of the most common chronic inflammatory skin diseases, affecting 1%–3% of the Caucasian population worldwide (Barker 1994; Christophers 1996). This complex disease is characterized by pathological changes in a variety of different cell types. These include epidermal keratinocyte hyperproliferation and altered differentiation as indicated by parakeratosis (nuclei in the stratum corneum), aberrant expression of the hyperproliferation-associated keratin pair 6/16 (Stoler et al. 1988; Weiss et al. 1984), involucrin and filaggrin (Bernard et al. 1986; Ishida-Yamamoto and Iizuka 1995), and integrin adhesion molecules (Hertie et al. 1992; Kellner et al. 1992). In addition, de novo expression of major histocompatibility complex (MHC) class II and intercellular adhesion molecule-1 (ICAM-1, CD54) by keratinocytes is observed (Barker et al. 1990; Nickoloff et al. 1990; Veale et al. 1995), i.e., molecules involved in interactions with immigrating T lymphocytes. Endothelial cells also are hyperproliferative, resulting in angiogenesis and dilation of dermal blood vessels, and express increased levels of ICAM-1, E-selectin (CD62E) and vascular cell adhesion molecule-1 (VCAM-1, CD106), as well as MHC class II, indicating activation (Detmar et al. 1994; Goodfield et al. 1994; Bjerke et al. 1988; Das et al. 1994). Finally, a mixed leukocytic infiltrate is seen composed of activated T lymphocytes (Ramirez-Bosca et al. 1988; Schlaak et al. 1994), neutrophils within the dermis and forming the telltale Munro’s microabscesses within the epidermis (Pinkus and Mehregan 1966), and an increased number of dermal mast cells and dendritic cells (Rothe et al. 1990; van de Kerkhof et al. 1995). A complex network of cytokines, chemokines, and other mediators is thought to mediate the psoriatic tissue alterations (Nickoloff 1991; Schon and Ruzicka 2001). Since its complex pathogenesis requires careful orchestration of sequential and highly specific leukocyte functions, psoriasis may serve as a model disease for studying the intertwined interactions of immigrating immune cells with resident epithelial and mesenchymal cells.