Céline GRECO

The skin is a highly complex organ responsible for sensation and protection, combining the immune and sensory systems in a ‘neuro-immuno-cutaneous endocrine' (NICE) system.

Hereditary palmoplantar keratoderma (HPK) is a genetic disorder characterised by focal hyperkeratosis, often associated with intense pain and an inflammatory response. Pain has a major impact on the daily lives of patients suffering from palmoplantar keratoderma. By specifically targeting the EGFR signalling pathway in Olmsted syndrome, a severe form of KPP linked to mutations in the TRPV3 channel, we have, for the first time, induced lasting remission of the disease in children who were severely disabled by its clinical manifestations, with the disappearance of hyperkeratosis and pain. Our project consists of studying the specific role of keratinocytes in the genesis of pain in these diseases.

A combined approach of gene expression and signalling pathway analyses in keratinocytes will help us understand how certain mutations can induce KPP and trigger pain and inflammation. We are studying two genetic diseases, Olmsted syndrome and epidermolysis bullosa simplex-Dowling Meara (mutation of keratins 5 and 14), two of the main symptoms of which are KPP and pain. Comparative analysis should lead to the identification of specific therapeutic targets.