Ex vivo culture of lesional psoriasis skin for pharmacological testing

• Published in: Journal of dermatological science Vol. 97; no. 2; pp. 109 - 116
• Main Authors: Tiirikainen, Minna Lund, Woetmann, Anders, Norsgaard, Hanne, Santamaria-Babí, Luis F., Lovato, Paola
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.02.2020
• Subjects: Ex vivo culture; Immunomodulation; Inflammation; Organ culture; Preclinical drug discovery; Psoriasis; IL; DAB; Psoriasis; DMSO; IHC; Immunomodulation; Ex vivo culture; Inflammation; TNF; BDP; K16; IFN-γ; Abs; Th; Preclinical drug discovery; CCL-20; Organ culture; hBD2; HSE; HE; DC; ELISA
• ISSN: 0923-1811; 1873-569X; 1873-569X
• DOI: 10.1016/j.jdermsci.2019.12.010

•Exogenous T cell stimulation results in functional, psoriasis specific in situ activation of resident T cells in ex vivo cultured psoriasis skin.•Resumed skin T cell activities recapitulate in bona fide the inflammatory environment found in psoriasis lesions in vivo.•Histopathological features are maintained during ex vivo culture.•The model offers a versatile tool for pharmacological testing as well as for investigating the inflammatory pathways of psoriasis. Psoriasis is a chronic, inflammatory skin disorder resulting from a complex interplay between immune and skin cells via release of soluble mediators. While a lot is known about the molecular mechanisms behind psoriasis pathogenesis, there is still a need for preclinical research models that accuratelyreplicate the disease. This study aimed to develop and characterize ex vivo culture of psoriasis skin as a model for pharmacological testing, where the immunological events of psoriasis can be followed. Full thickness punch biopsies of lesional psoriasis skin were cultured in submerged conditions up to 144 h followingin situ T cell stimulation with rhIL-23 and anti-CD3 and anti-CD28 antibodies. The T cell mediated skin inflammation was assessed by gene and protein l analysis for a panel of inflammatory mediators. Tissue integrity and morphology were evaluated by histological analysis. T cell stimulation resulted in functional and psoriasis specificin situ activation of T cells. The expression levels of most of the proinflammatory mediators related to both immune and skin cells were comparable to these in freshly isolated tissue at 48 and 96 h of culture. Tissue integrity and morphology were sustained up to 96 h. Treatment with a corticosteroid reduced the expression of several pro-inflammatory cytokines and chemokines, whereas anti-IL-17A antibody treatment reduced the expression of the IL-17A downstream markers IL-8 and DEFB4. By preserving keyimmunopathological mechanisms of psoriasis, ex vivo culture of psoriasis skin can be used for the investigation of inflammatory processes of psoriasis and for preclinical drug discovery research.