Ex vivo culture of lesional psoriasis skin for pharmacological testing. Issue 2 (February 2020)

• Record Type: Journal Article
• Authors: Tiirikainen, Minna Lund; Woetmann, Anders; Norsgaard, Hanne; Santamaria-Babí, Luis F.; Lovato, Paola
• Is Part Of: Journal of dermatological science. Volume 97:Issue 2(2020)
• Page Start: 109
• Page End: 116
• Publication Date: 2020-02
• Subjects: DC dendritic cell -- IL- interleukin- -- Th cell T helper cell -- TNF tumor necrosis factor -- IFN-γ interferon-γ -- CCL-20 chemokine (C-C motif) ligand-20 -- hBD2 human beta defensin 2 -- HSE human skin equivalent -- DMSO dimethyl sulfoxide -- ELISA enzyme linked immunosorbent assay -- IHC immunohistochemical -- DAB diaminobenzidine -- Abs antibodies -- K16 keratin 16 -- BDP betamethasone dipropionate -- HE Hematoxylin and eosin; Psoriasis -- Ex vivo culture -- Organ culture -- Inflammation -- Immunomodulation -- Preclinical drug discovery; Dermatology -- Periodicals; Skin Diseases -- Periodicals; Dermatologie -- Périodiques; 616.5005
• DOI: 10.1016/j.jdermsci.2019.12.010
• Languages: English
• ISSNs: 0923-1811

Abstract

Highlights: 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. Abstract: Background: 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. Objective: 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. Methods: Full thickness punch biopsies of lesional psoriasis skin were cultured in submerged conditions up to 144 h following in 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. Results: T cell stimulation resulted in functional and psoriasis specific in 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 . Conclusion: 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.