Significance
This study shows that keratinocytes extracted from patients' psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release.
Statement of significance
This study shows that keratinocytes extracted from patients' psoriatic skin retain, at least in part, the disease phenotype. Indeed, when combined in a 3D model of tissue-engineered psoriatic skin, keratinocytes exhibited a higher proliferation rate, and produced a thicker epidermis than a healthy skin control. In addition, their hyperproliferation was aggravated by a treatment with CGRP, a neuropeptide released by sensory nerves. In a innervated model of tissue-engineered psoriatic skin, an increase in keratinocyte hyperproliferation was also observed after inducing neurons to release neuropeptides. This effect was prevented by concomitant treatment with an antagonist to CGRP. Thus, this study shows that sensory nerves can directly participate to affect keratinocyte hyperproliferation in psoriasis through CGRP release.