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MALT1 targeting suppresses CARD14‐induced psoriatic dermatitis in mice

Elien Van Nuffel (UGent) , Jens Staal (UGent) , Griet Baudelet (UGent) , Mira Haegman (UGent) , Yasmine Driege (UGent) , Tino Hochepied (UGent) , Inna Afonina (UGent) and Rudi Beyaert (UGent)
(2020) EMBO REPORTS. 21(7).
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Abstract
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-κB 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 CARD14E138A 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 CARD14E138A 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.
Keywords
Genetics, Biochemistry, Molecular Biology, cytokines, inflammation, MALT1, psoriasis, therapeutic, PARACASPASE MALT1, PROTEOLYTIC ACTIVITY, CELL, PATHOGENESIS, ACTIVATION, MUTATIONS, PROTEASE, CARD14, INACTIVATION, RESPONSES

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MLA
Van Nuffel, Elien, et al. “MALT1 Targeting Suppresses CARD14‐induced Psoriatic Dermatitis in Mice.” EMBO REPORTS, vol. 21, no. 7, 2020, doi:10.15252/embr.201949237.
APA
Van Nuffel, E., Staal, J., Baudelet, G., Haegman, M., Driege, Y., Hochepied, T., … Beyaert, R. (2020). MALT1 targeting suppresses CARD14‐induced psoriatic dermatitis in mice. EMBO REPORTS, 21(7). https://doi.org/10.15252/embr.201949237
Chicago author-date
Van Nuffel, Elien, Jens Staal, Griet Baudelet, Mira Haegman, Yasmine Driege, Tino Hochepied, Inna Afonina, and Rudi Beyaert. 2020. “MALT1 Targeting Suppresses CARD14‐induced Psoriatic Dermatitis in Mice.” EMBO REPORTS 21 (7). https://doi.org/10.15252/embr.201949237.
Chicago author-date (all authors)
Van Nuffel, Elien, Jens Staal, Griet Baudelet, Mira Haegman, Yasmine Driege, Tino Hochepied, Inna Afonina, and Rudi Beyaert. 2020. “MALT1 Targeting Suppresses CARD14‐induced Psoriatic Dermatitis in Mice.” EMBO REPORTS 21 (7). doi:10.15252/embr.201949237.
Vancouver
1.
Van Nuffel E, Staal J, Baudelet G, Haegman M, Driege Y, Hochepied T, et al. MALT1 targeting suppresses CARD14‐induced psoriatic dermatitis in mice. EMBO REPORTS. 2020;21(7).
IEEE
[1]
E. Van Nuffel et al., “MALT1 targeting suppresses CARD14‐induced psoriatic dermatitis in mice,” EMBO REPORTS, vol. 21, no. 7, 2020.
@article{8661448,
  abstract     = {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-κB 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 CARD14E138A 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 CARD14E138A 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.},
  articleno    = {e49237},
  author       = {Van Nuffel, Elien and Staal, Jens and Baudelet, Griet and Haegman, Mira and Driege, Yasmine and Hochepied, Tino and Afonina, Inna and Beyaert, Rudi},
  issn         = {1469-221X},
  journal      = {EMBO REPORTS},
  keywords     = {Genetics,Biochemistry,Molecular Biology,cytokines,inflammation,MALT1,psoriasis,therapeutic,PARACASPASE MALT1,PROTEOLYTIC ACTIVITY,CELL,PATHOGENESIS,ACTIVATION,MUTATIONS,PROTEASE,CARD14,INACTIVATION,RESPONSES},
  language     = {eng},
  number       = {7},
  pages        = {12},
  title        = {MALT1 targeting suppresses CARD14‐induced psoriatic dermatitis in mice},
  url          = {http://dx.doi.org/10.15252/embr.201949237},
  volume       = {21},
  year         = {2020},
}

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