Molecular determinants of inflammation

Psoriasis is a common immune-mediated disease which affects about 1 % of the European population. The disease presents with cutaneous inflammation caused by aberrant epidermal differentiation. Currently there is no effective treatment for psoriasis and the visible marks of the disease greatly impact patients' physical and psychosocial life style.

Scientists on the EU-funded (RHOA IN INFLAMMATION) (Role of a small GTPase, RhoA, in skin inflammation) project set out to shed light into the molecular aetiology of the disease. The work focused in particular on the role of the small GTPase RhoA, which has a central function in the organisation of the actin cytoskeleton.

Researchers obtained transgenic mice with a specific deletion of RhoA in keratinocytes and performed gene expression analysis. They found that RhoA altered the expression of over 60 genes including a few linked to psoriasis. One of the key pathways affected by RhoA was retinoic acid signalling and especially the first steps of retinol metabolism.

Retinoic acid signalling is known to affect skin tumour formation. Hence, the consortium tested the incidence of skin cancer in mice with a keratinocyte-restricted deletion of the RhoA gene. As expected, they observed that skin tumour formation was strongly altered in these animals, underscoring the role of RhoA in skin homeostasis.

Taken together, the activities of the RHOA IN INFLAMMATION project have provided significant knowledge on the regulation of skin sensitivity to inflammatory stress in vivo. The results have therapeutic implications and could be utilised for the design of targeted interventions against psoriasis.