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

Kurgyis, Z., Vornholz, L., Pechloff, K., Kemeny, L.V., Wartewig, T., Muschaweckh, A., Joshi, A., Kranen, K., Hartjes, L., Mockel, S., Steiger, K., Hameister, E., Volz, T., Mellett, M., French, L.E., Biedermann, T., Korn, T., Ruland, J. (2021). Sci Immunol 6, eabi4425.



BCL10 and MALT1 form ubiquitously expressed signalosomes that control immune and inflammatory pathways in many tissues. Pathological interplay between the immune system and keratinocytes is known to drive pathogenesis in psoriasis; however, the molecular and cellular functions of BCL10/MALT1 in the complex pathogenesis of psoriasis are not well defined. Kurgyis et al. engineered mouse models to specifically activate, inactivate, or attenuate BCL10/MALT1 signaling specifically in keratinocytes. They identified that BCL10 and MALT1 function to initiate and amplify keratinocyte responses to inflammatory cytokines and that constitutive activation of BCL10/MALT1 signaling in keratinocytes is sufficient to drive psoriasis. Furthermore, BCL10/MALT1 signaling is frequently altered in human psoriasis patients, suggesting that targeting the BCL10/MALT1 signalosome using MALT1 inhibitors may be a promising therapeutic approach to treat psoriasis.