TESTING 29


vivo. These can be attenuated by depigmenting factors such as kojic acid. A model of pigmentary spots induced or accentuated by components of urban pollution is currently under development. Vitiligo is a chronic autoimmune disease of


the epidermis. It is characterised by a loss of melanocytes resulting in white spots or area on the skin, of variable size, appearance and location, which tend to enlarge. The loss of pigmentation is thought to be due to detachment of melanocytes from the basal layer and their apoptosis, induced by an excess of type-I cytokines such as IFN-γ and TNF-α produced by an exacerbated response of self- reactive CD8 lymphocytes. These cytokines induce an overproduction of matrix metalloproteinase 9 (MMP-9) by the keratinocytes which causes the cleavage of E- cadherin, a melanocyte anchoring molecule in the basal layer of the epidermis.20 In vitro, the stimulation of RHE by these two


cytokines results in the characteristic detachment of melanocytes that can be observed by immunostaining in the supra-basal layers, an increase in MMP-9 and in the soluble form of E-cadherin.


Simple and relevant models In conclusion, since the 1970s, modelling skin in 3D has remarkably evolved to complement information provided from monolayer cell cultures. As close representative of the in vivo physiology, 3D skin models are now considered as essential tools to fully understand the skin biology in all its states since the combination of reconstructed epidermis and selected cellular mediators such as cytokine cocktails or growth factors, allows the modelling of various inflammatory pathologies or pigmentary disorders. This very simple conceptual approach, in which the experimenter plays the role of the immune system or paracrine communication, makes it possible to demonstrate in vitrothe effects of therapeutic or preventive compounds in a low or medium-throughput format, to identify their targets and to study the mechanisms of action involved using cellular and molecular biology techniques.


PC


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6 van den Bogaard E, Ilic D, Dubrac S, et al. Perspective and Consensus Opinion: Good Practices for Using Organotypic Skin and Epidermal Equivalents in Experimental Dermatology Research. J Invest Dermatol. 2020;


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13 Ishikawa J, Narita H, Kondo N, Hotta M, Takagi Y, Masukawa Y, et al. Changes in the ceramide profile of atopic dermatitis patients. J Invest Dermatol. 2010;130(10):2511-4.


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15 Tawada C, Kanoh H, Nakamura M, Mizutani Y, Fujisawa T, Banno Y, et al. Interferon-γdecreases ceramides with long-chain fatty acids: possible involvement in atopic dermatitis and psoriasis. J Invest Dermatol. 2014;134(3):712-8.


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20 Boukhedouni N, Martins C, Darrigade A-S, et al. Type-1 cytokines regulate matrix metalloprotease-9 production and E-cadherin disruption to promote melanocyte loss in vitiligo. JCI Insight. 5 2020;


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