MALT1 protease activity controls the expression of inflammatory genes in keratinocytes upon zymosan stimulation.

The protease activity of the paracaspase MALT1 plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor NF-κB and is thus essential for the expression of inflammatory target genes. MALT1 is not only present in cells of the hematopoietic lineage, but is ubiquitously expressed. Here we report that stimulation with zymosan or S. aureus induced MALT1 protease activity in human primary keratinocytes. Inhibition of the Src family of kinases or novel PKC isoforms as well as silencing of CARMA2 or BCL10 interfered with activation of MALT1 protease. Silencing or inhibition of MALT1 protease strongly decreased the expression of important inflammatory genes such as TNFα, IL17C, CXCL8 and HBD-2. MALT1 inhibited cells were unable to mount an antimicrobial response upon zymosan stimulation or phorbolester/ionomycin-treatment, demonstrating a central role of MALT1 protease activity in keratinocyte immunity and suggesting MALT1 as a potential target in inflammatory skin diseases.