Upregulation of RANTES in psoriatic keratinocytes: a possible pathogenic mechanism for psoriasis

Intraepidermal collections of neutrophils and lymphocytes are unique featur es of the inflammatory 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-alpha and MCP-1 ha ve been reported in the keratinocytes of psoriatic tissue, IL-8 and GRO-alp ha belong to a subfamily (C x C) class and MCP-1 is a beta chemokine, In th is study, we investigated RANTES, which is a beta chemokine (C-C class); RA NTES has been found to be associated with various cell-mediated hypersensit ive disorders. We obtained eight skin biopsies from chronic psoriatic plaqu es, and five biopsies each from non-lesional psoriatic skin, lichen planus, eczematous dermatitis and skin from healthy controls. Snap-frozen samples were cut into 7 mu m cryosections and stained with 6 mg/ml of monoclonal an ti-RANTES mouse IgG (DNAX, Palo Alto, CA). Standard immunohistochemistry te chniques were applied. RANTES was detected only in the keratinocytes. The n umber of keratinocytes in per mm(2) of epidermis stained for RANTES were 11 6.79+/-98.42 in psoriatic tissues compared to 32.00+/-46.05 (p<0.05), 6.39/-3.59 (p<0.01), 2.64+/-1.15 (p<0.01) and 3.53+/-5.26 (p<0.01), respectivel y, in the nonlesional, lichen planus, eczematous lesions and normal skin. T his is the first study to report that the keratinocytes of psoriatic tissue express high levels of RANTES compared to the controls. IL-8 and related m olecules (C x C class) are predominantly chemotactic for neutrophils and MC P-1 is a strong chemotactic factor for monocytes, In contrast, RANTES is ch emotactic for memory T cells and activated naive T cells. Increased amounts of RANTES as reported here provide an explanation for migration of the act ivated T cells to the epidermis of the psoriatic lesions. In addition, RANT ES activates T cells. These results suggest that RANTES may have a signific ant role in the inflammatory process of psoriasis, Our findings further sub stantiate a regulatory role for keratinocytes in the inflammatory process o f psoriasis.