Upregulation of RANTES in Psoriatic Keratinocytes: a Possible Pathogenic Mechanism for Psoriasis

Intraepidermal collections of neutrophils and lymphocytes are unique features of the in£ammatory reaction of psoriasis. Migration of leukocytes from dermis to the epidermis suggests a role for chemotactic agent(s). In recent years, increased levels of chemokines such as IL-8 , GRO-a and MCP-1 have been reported in the keratinocytes of psoriatic tissue. IL-8 and GRO-a belong to a subfamily (C6C) class and MCP-1 is a b chemokine. In this study, we investigated RANTES, which is a fi chemokine (C-C class); RANTES has been found to be associated with various cell-mediated hypersensitive disorders.We obtained eight skin biopsies from chronic psoriatic plaques, and ¢ve biopsies each from nonlesional psoriatic skin, lichen planus, eczematous dermatitis and skin from healthy controls. Snap-frozen samples were cut into 7 mm cryosections and stained with 6 mg/ml of monoclonal anti-RANTES mouse IgG (DNAX, Palo Alto, CA). Standard immunohistochemistry techniques were applied. RANTES was detected only in the keratinocytes. The number of keratinocytes in per mm 2 of epidermis stained for RANTES were 116.79i98.42 in psoriatic tissues compared to 32.00i46.05 (pv0.05), 6.39i3.59 (pv0.01), 2.64i1.15 (pv0.01) and 3.53i5.26 (pv0.01), respectively, in the nonlesional, lichen planus, eczematous lesions and normal skin. This is the ¢rst study to report that the keratinocytes of psoriatic tissue express high levels of RANTES compared to the controls. IL-8 and related molecules (C6C class) are predominantly chemotactic for neutrophils and MCP-1 is a strong chemotactic factor for monocytes. In contrast, RANTES is chemotactic for memory T cells and activated naive T cells. Increased amounts of RANTES as reported here provide an explanation for migration of the activated T cells to the epidermis of the psoriatic lesions. In addition, RANTES activates T cells. These results suggest that RANTES may have a signi¢cant role in the in£ammatory process of psoriasis. Our ¢ndings further substantiate a regulatory role for keratinocytes in the in£ammatory process of psoriasis.Key words: fi chemokine; chemotaxis; cutaneous in£ammation.