Monday 21 Jan 2013Critical role of Th17 proinflammatory cytokines in skin inflammation: in vitro, ex vivo and in vivo translational models

Prof Jean-Claude Lecron - Université et CHU de Poitiers, France

Harrison 004 15:00-16:00

By studying the role of cytokines in tissue inflammation induction mechanisms and interactions between inflammatory and keratinocytes, we highlighted the key role of a number of cytokines (IL-17 and IL-22, Oncostatin M (OSM), TNF and IL-1) on keratinocytes to induce an inflammatory phenotype including increased anti-bacterial activities, and cell differentiation inhibition. Using transcriptomic approaches, we demonstrated that the biological effects of each of these cytokine are unique, and that huge synergistic effects are observed when these cytokines are added together, even at low concentrations.
We further reported a strong cytokine deregulation defining specific signatures in inflammatory skin diseases such as psoriasis, atopic dermatitis or necrotizing vasculitis, that we model in vitro. The requirement of proof of concept of the key role of these cytokines in skin inflammation leads us to use animal models to complete in vitro and ex vivo studies. Depending on experimental stress, we induce skin inflammation either with or without Th17 cytokines. In this context, we contributed to the characterization of Th17 lymphocytes in human pathological conditions and highlighted the role of epithelial cells as bonafide inflammatory cells, potential downstream targets to treat chronic inflammation.

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