Psoriasis arises from poorly defined pathological crosstalk between keratinocytes and the immune system. BCL10 and MALT1 are ubiquitously expressed inflammatory signalling proteins that can interact with the psoriasis susceptibility factor CARD14, but their functions in psoriasis are insufficiently understood. To explore the roles of BCL10 and MALT1 in inflammatory skin diseases, we engineered a series of conditional mouse mutants to specifically activate, inactivate or attenuate BCL10/MALT1 signalling in keratinocytes in vivo. We report that although keratinocyte-intrinsic BCL10/MALT1 deletions completely rescue inflammatory skin pathology triggered by germline Card14 gain-of-function mutation in mice, the BCL10/MALT1 signalosome is surprisingly not involved in the CARD14-dependent IL-17R proximal pathway. Instead, it plays a more pleiotropic role by amplifying keratinocyte responses to a series of inflammatory cytokines, including IL-17A, IL-1b and TNF. Moreover, selective keratinocyte-intrinsic activation of BCL10/MALT1 signalling with an artificial engager molecule is sufficient to initiate lymphocyte-mediated psoriasiform skin inflammation. Furthermore, we found aberrant BCL10/MALT1 activity in the skin of human sporadic psoriasis patients. Together, these results establish that BCL10/MALT1 signalosomes can act as initiators and crucial amplifiers of psoriatic skin inflammation and indicate a critical function for this complex in sporadic psoriasis.

ESDR333 - Keratinocyte-intrinsic BCL10/MALT1 activity initiates and amplifies psoriasiform skin inflammation

The scientific meeting of the European Society for Dermatological Research (ESDR) is held yearly, usually in September. With an international attendance of more than 1000 skin scientists from around the globe, the four-day event includes short oral presentations from peer-reviewed abstracts, keynote lectures from international experts, sponsored symposia, satellite programs, educational events as well as an important focus on posters, networking and building collaborations amongst scientists. For more information about this year’s meeting visit our website.