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Keratinocyte-derived IL-17E contributes to inflammation in psoriasis |
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Published in | Journal of investigative dermatology. 2016, vol. 136, no. 10, p. 1970-1980 | |
Abstract | Psoriasis is a chronic inflammatory skin disorder effectively treated by blocking IL-17RA, a receptor chain used by several IL-17 family members, including IL-17E. While IL-17A is critically involved in the pathogenesis of psoriasis, the contribution of IL-17E remains unknown. Here we demonstrate that IL-17E+ cells are more abundant than IL-17A+ cells in lesional psoriatic skin. IL-17E synthesis is increased in keratinocytes within psoriatic plaques, and macrophages having a mixed M1/M2 phenotype represent an important proportion of the IL-17E+ cells infiltrating the dermis. Mechanistically, macrophages do not synthetize but rather uptake IL-17E via receptor-mediated clathrin-dependent endocytosis. Furthermore, monocyte-derived macrophages in-vitro polarized in M2, but not M1, express the IL-17E receptor and respond to IL-17E by preferentially producing inflammatory cytokines and chemokines involved in neutrophils recruitment. Remarkably, IL-17E expression in lesional psoriatic skin correlates with the number of neutrophils while being inversely proportional to the number of infiltrating T cells. These data provide strong evidence for a pro-inflammatory role of keratinocyte-derived IL-17E in psoriasis, possibly via macrophage activation. | |
Identifiers | PMID: 27329229 | |
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Research groups | La matrice extracellulaire (651) Mécanismes des pathologies de l'inflammation cutanée (919) | |
Citation (ISO format) | SENRA, Luisa et al. Keratinocyte-derived IL-17E contributes to inflammation in psoriasis. In: Journal of investigative dermatology, 2016, vol. 136, n° 10, p. 1970-1980. doi: 10.1016/j.jid.2016.06.009 https://archive-ouverte.unige.ch/unige:85354 |