| First Author | Van Nuffel E | Year | 2020 |
| Journal | EMBO Rep | Volume | 21 |
| Issue | 7 | Pages | e49237 |
| PubMed ID | 32343482 | Mgi Jnum | J:292094 |
| Mgi Id | MGI:6445462 | Doi | 10.15252/embr.201949237 |
| Citation | Van Nuffel E, et al. (2020) MALT1 targeting suppresses CARD14-induced psoriatic dermatitis in mice. EMBO Rep 21(7):e49237 |
| abstractText | CARD14 gain-of-function mutations cause psoriasis in humans and mice. Together with BCL10 and the protease MALT1, mutant CARD14 forms a signaling node that mediates increased NF-kappaB signaling and proinflammatory gene expression in keratinocytes. However, it remains unclear whether psoriasis in response to CARD14 hyperactivation is keratinocyte-intrinsic or requires CARD14 signaling in other cells. Moreover, the in vivo effect of MALT1 targeting on mutant CARD14-induced psoriasis has not yet been documented. Here, we show that inducible keratinocyte-specific expression of CARD14(E138A) in mice rapidly induces epidermal thickening and inflammation as well as increased expression of several genes associated with psoriasis in humans. Keratinocyte-specific MALT1 deletion as well as oral treatment of mice with a specific MALT1 protease inhibitor strongly reduces psoriatic skin disease in CARD14(E138A) mice. Together, these data illustrate a keratinocyte-intrinsic causal role of enhanced CARD14/MALT1 signaling in the pathogenesis of psoriasis and show the potential of MALT1 inhibition for the treatment of psoriasis. |
