Keratinocytes are the predominant cell type in the epidermis, the outermost layer of the skin. When activated, they can stimulate cutaneous inflammation and abnormal keratinocyte behavior plays a role in the pathogenesis of psoriasis. Psoriasis is an inflammatory disease that affects skin and other organs and leads to impaired quality of life. Approximately 2 to 3% of the worldwide population suffers from this debilitating condition, the origins and causes of which are currently poorly
understood. Recently, the CARMA2 gene has been identified as a psoriasis susceptibility gene. Little is known about the biochemical function and physiological role of the CARMA2 protein. We have obtained evidence for a role of the paracaspase MALT1 in CARMA2 mediated pro-inflammatory signaling in keratinocytes. The aim of this project is to further unravel the CARMA2/MALT1-mediated signaling cascade in keratinocytes and to characterize the specific role of MALT1 and CARMA2 in the pathogenesis of psoriasis using mouse genetic engineering and mouse models of skin inflammation.