Morphological features induced by interleukin 17 in a 3D organotypic cultures of normal human skin are promptly reverted by a specific biological inhibitor

Abstract

Psoriatic plaque is the result of a strict interaction among epidermal cells, immune sys- tem, and soluble cytokines. Interleukin 17 (IL-17) is a well-known proinflammatory psoriatic cytokine mainly produced by the T helper subclass Th17. In the last decade we standardized a 3D model organotypic cultures of normal human skin for studying the early, intrinsic and spe- cific effects induced by IL-17. We demonstrated that IL-17 elicited Langerhans cell (LC) activa- tion and migration, keratin 17 expression, Toll like receptor 7 and 9 expressions and profoundly altered filaggrin expression, without affecting the suprabasal distribution of keratin 10 and ker- atin 14. Moreover, this cytokine early inhibited keratinocyte proliferation, strongly suggesting that this event can be the basis for the response to injury leading to the psoriatic characteris- tic hyperproliferation observed in lesional plaques. In the present study, we incubated bioptic skin fragments obtained after aesthetic surgery of healthy young women (n=5) with i) IL-17 alone, ii) with a combination of IL-17 and an IL-17 biological inhibitor, iii) with the IL-17 bio- logical inhibitor alone. Control samples were in parallel cultured. Incubation lasted for 24 and 48 hours with skin at the air-liquid interface. Immunofluorescence experiments and transmis- sion electron microscopy (TEM) analysis were carried out. Samples incubated with the IL-17 biological inhibitor were comparable to controls. By immunofluorescence, the combination reverted IL-17-induced effects at all considered time-points. By TEM, LCs appeared less acti-vated as shown by the paucity of Birbeck granules and the highly dispersed nuclear chromatin. The epidermal ultrastructure was comparable in all groups, with well-preserved desmosomes, interspersed keratin filaments and terminally differentiated granular keratinocytes/corneocytes. These results highlight the clinical usefulness of this experimental approach for identifying the early psoriatic processes that can be modulated by last generation biological agents.