Psoriasis is a common chronic skin disease characterized by a pro-inflammatory environment mediated by keratinocytes and both innate and adaptative immune responses. This inflammation is mostly driven by the IL-17/IL-23 axis resulting in the production of inflammatory and immune factors (chemokines and antimicrobial peptides) by keratinocytes. These mediators lead to an amplification loop and consequently to an epidermal hyperplasia. To our knowledge, very few 3D skin models involving lymphocyte T-helper cell type 17 (LTh17) reproduce accurately psoriasis features. The aim of this work was to develop an immunocompetent skin model reproducing the biological characteristics of psoriatic lesional skin. As psoriasis physiopathology is mostly mediated by the interplay of LTh17 and keratinocytes, we developed a 3D model that integrated both of these cell types. To this purpose, LTh17 were differentiated from naive T cells and rigorously characterized. Using ELISA assay and flow cytometry, we confirmed the functional differentiation of LTh17 with relevant production of Th17 cytokines (IL-17A and IL-17F). Then, LTh17 were co-cultured with a reconstructed epidermis. Our immunocompetent 3D model recapitulated inflammatory features of psoriasis with the secretion of characteristic cytokines (IL-17A, IL-17F), chemokines (CXCL1, CXCL8, CCL20) and antimicrobial peptide (S100A7). At last, our psoriasis-mimicking skin model showed an alteration of keratinocyte differentiation leading to epidermal morphological changes (acanthosis). The model’s functionality was assessed and confirmed using an anti-IL-17A neutralizing antibody. Thanks to the communication between LTh17 and keratinocytes, this compromised 3D model succeeded in reproducing psoriatic characteristics, including keratinocyte differentiation defects and dysregulation of the inflammatory response. This immunocompetent 3D psoriasis model could be suitable for the screening of natural therapeutic molecules dedicated to psoriasis treatment.

ESDR351 - Development and characterization of an immune 3D model mimicking psoriasis

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.