New pathogenetic inflammatory mechanisms in psoriasis. Relevance in anti-IL-17 biological therapy.

Proponente Giovanna Romeo - Professore Associato
Sottosettore ERC del proponente del progetto
Componenti gruppo di ricerca
Componente Categoria
Giorgio Mangino Componenti il gruppo di ricerca
Concetta Potenza Componenti il gruppo di ricerca
Componente Qualifica Struttura Categoria
Serena Fragiotta dottorando scienze e biotecnologie medico-chirurgiche Altro personale Sapienza o esterni

Psoriasis is a chronic inflammatory skin disease affecting about 2% of the Western population, caused by the excessive secretion of inflammatory cytokines. Deregulation of the IL-23/IL-17 axis allows the activation of Th-17 T cells subset and, by consequence, the reprogramming of keratinocytes proliferative response. This induces the secretion of several cyto-/chemokines and antimicrobial peptides by the keratinocytes. The induction of specific chemotactic factors recruits myeloid dendritic cells, Th17 lymphocytes and neutrophils to the lesion site. Currently, one anti-IL-17 biological agent (Secukinumab) is approved for the treatment. Psoriasis-associated inflammation can also affect vascular and systemic functions associated with several extracutaneous manifestations.
Beside cell-to-cell contacts and the release of cytokines, hormones and second messengers, it has been recently demonstrated the ability of cells to communicate each other through the release of different types of extracellular vesicles containing DNA, RNA, microRNAs and proteins, able to modulate the function of the receiving cells. Even if it has been reported the alteration of microvesicles trafficking in several diseases ranging from viral and microbial infections to hematological and non-hematological malignancies, there is scarce evidence of the involvement of microvesicles trafficking in the pathogenesis of psoriasis. Preliminary results obtained in our laboratory indicate that IL-17A is able to modify, both qualitatively and quantitatively, the extracellular vesicles cargo and release.
In this respect, this project, based on multidisciplinary research approaches, is aimed to hopefully draw clinically relevant conclusions about new biomarkers development and their extracellular delivery in psoriasis.


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