Overview of the molecular determinants contributing to the expression of Psoriasis and Psoriatic Arthritis phenotypes
Valerio Caputo, Claudia Strafella, Andrea Termine, Annunziata Dattola, Sara Mazzilli, Caterina Lanna, Terenzio Cosio, Elena Campione, Giuseppe Novelli, Emiliano Giardina, Raffaella Cascella
Abstract
Psoriasis and psoriatic arthritis are multifactorial chronic disorders whose etiopathogenesis essentially derives from the alteration of several signalling pathways and the co-occurrence of genetic, epigenetic and non-genetic susceptibility factors that altogether affect the functional and structural property of the skin. Although shared and differential susceptibility genes and molecular pathways are known to contribute to the onset of pathological phenotypes, further research is needed to dissect the molecular causes of psoriatic disease and its progression towards Psoriatic Arthritis. This review will therefore be addressed to explore differences and similarities in the etiopathogenesis and progression of both disorders, with a particular focus on genes involved in the maintenance of the skin structure and integrity (keratins and collagens), modulation of patterns of recognition (through Toll-like receptors and dectin-1) and immuno-inflammatory response (by NLRP3-dependent inflammasome) to microbial pathogens. In addition, special emphasis will be given to the contribution of epigenetic elements (methylation pattern, non-coding RNAs, chromatin modifiers and 3D genome organization) to the etiopathogenesis and progression of psoriasis and psoriatic arthritis. The evidence discussed in this review highlights how the knowledge of patients' clinical and (epi)genomic make-up could be helpful for improving the available therapeutic strategies for psoriasis and psoriatic arthritis treatment.