Up-regulation of the chemokine CCL21 in the skin of subjects exposed to irritants

Eleven normal individuals were challenged with different chemical or physical irritants. Two patients with Allergic Contact Dermatitis (ACD) were also challenged with the relevant antigen in order to have a positive control for CCL21 expression. Macroscopic as well as microscopic responses were evaluated. We observed typical ICD responses with mostly mononuclear cells in perivascular areas, but a predominance of polymorphonuclear cells away from the inflamed blood vessels and in the epidermis at 24 hours. Immunohistochemical studies showed up-regulation of CCL21 by lymphatic endothelial cells in all the biopsies taken from ICD and ACD lesions compared to normal skin. Kinetic study at 10, 48, 96 and 168 hours after contact with a classical irritant (sodium lauryl sulphate) showed that the expression of CCL21 was increased in lymphatic vessels at 10 hours, peaked at 48 hours, and then gradually declined. There was a strong correlation between CCL21 expression and the macroscopic response (r = 0.69; p = 0.0008), but not between CCL21 and the number of infiltrating cells in the lesions.These results provide new evidence for the role of CCL21 in inflammatory processes. Since the up-regulation of this chemokine was observed in ICD and ACD, it is tempting to speculate that this mechanism operates independently of the type of dermal insult, facilitating the emigration of CCR7+ cells.Skin derived Dendritic cells (DC) such as Langerhans cells (LC) and interstitial DC play vital roles in immune surveillance because they have efficient uptake and antigen presentation mechanisms. Antigens are captured and processed, and few hours later DC reach peripheral lymph nodes (PLN) via afferent lymphatics [1].The molecular mechanisms that regulate DC emigration are not fully understood. It seems to depend on the selective responsiveness of DC to special sets of signals. Cytokines such as IL-1β, TNF-α, IL-18 [2], CCL19 [3], and other molecules like Osteopontin [4], MMPs [5], prostaglandin