Experimentally induced psoriatic lesion associates with interleukin (IL)-6 in mast cells and appearance of dermal cells expressing IL-33 and IL-6 receptor

Abstract

Mast cells are involved in the development of psoriatic lesion, but it is not known how mast cells are activated or whether mast cell cytokines are expressed during the lesion development. In this study, the Köbner reaction was induced in uninvolved psoriatic skin of 18 patients using the tape-stripping technique, and a sequence of biopsies was collected at 0 days, 2 h and 3 days or at 0 days, 1 day and 7 days for histochemical analysis. Eight patients developed the Köbner reaction verified at the follow-up visit 2-2·5 weeks later. No significant differences were observed in total tryptase(+) mast cells, psoriasis area and severity index and age/sex. Instead, the percentage of tryptase(+) mast cells showing interleukin (IL)-6 immunoreactivity was significantly higher in biopsies from Köbner-positive patients than in those from Köbner-negative patients. IL-33 is a known inducer of IL-6 in mast cells, and the number of IL-33(+) cells increased significantly in Köbner-positive dermal skin at days 3-7. The number of dermal cells with IL-6 receptor (IL-6R, CD126) also increased in Köbner-positive skin at days 3-7. Unexpectedly, the number of IL-6R(+) cells was even higher in Köbner-negative skin at days 3-7. In the chronic plaque of 10 other psoriatic patients, the numbers of IL-6(+) mast cells and dermal cells showing IL-6R were higher than those in the non-lesional skin. In conclusion, the positive Köbner reaction is associated with IL-6 in mast cells and appearance of IL-6R(+) and IL-33(+) dermal cells. This suggests that a previously unrecognized vicious circle may develop in the early psoriatic lesion.

Fig. 1

Localization of interleukin (IL)-6 in tryptase-positive mast cells in psoriatic skin using the sequential double-staining technique. The skin cryosection was stained first (a,c) enzyme-histochemically for tryptase. After photographing, the red staining product was dissolved away with 15% Tween20 overnight followed by (b,d) staining immunohistochemically for IL-6 and re-photographing. (a,b) Non-lesional psoriatic skin at day 0; (c,d) Köbner-positive psoriatic skin at day 3.

Fig. 2

Immunohistochemical staining of interleukin (IL)-6 receptor in a Köbner-negative skin biopsy taken at day 7 after the tape-stripping.

Fig. 3

Immunohistochemical staining of interleukin (IL)-33 in a 7-day-old psoriatic lesion (Köbner-positive skin). Note that the IL-33 staining is predominantly nuclear in the epidermis, but both nuclear and cytoplasmic stainings are seen in the dermis.