CARD14-Mediated Activation of Paracaspase MALT1 in Keratinocytes: Implications for Psoriasis

Nuffel, Elien Van; Schmitt, Anja; Afonina, Inna S.; Schulze‐Osthoff, Klaus; Beyaert, Rudi; Hailfinger, Stephan

doi:10.1016/j.jid.2016.09.031

Cited by 33 publications

(29 citation statements)

References 69 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, activating mutations in the CARMA2-encoding gene CARD14 have been found to be associated with development of psoriasis, an inflammatory skin disease, in human patients (122, 123). Since then, an increasing number of studies have reported genetic mutations in CARD14 associated to psoriasis diseases (124). Some of the CARD14 mutations found in patients were shown to enhance NF-κB activation and promote secretion of CCL20 and IL-8, two chemokines known to be associated with psoriasis (123, 124).…”

Section: Malt1 Deregulation Is Associated With Allergy Inflammatory mentioning

confidence: 99%

“…Since then, an increasing number of studies have reported genetic mutations in CARD14 associated to psoriasis diseases (124). Some of the CARD14 mutations found in patients were shown to enhance NF-κB activation and promote secretion of CCL20 and IL-8, two chemokines known to be associated with psoriasis (123, 124). Similar to CARD11 mutations associated with lymphoid malignancies, CARD14 mutations were mostly found in the CC region.…”

Section: Malt1 Deregulation Is Associated With Allergy Inflammatory mentioning

confidence: 99%

“…This raises the interesting possibility that, at least in the context of cancer, MALT1 inhibitors may exert their effects by a dual action on both the inhibition of the growth of cancer cells and boosting anti-tumor immune responses. Another possible field of application for MALT1 inhibitors are inflammatory skin diseases such as psoriasis, in which inhibitory effects on keratinocytes and possibly on skin T cells may benefit the patients (15, 124–126). As we progress in our knowledge about the molecular and biological function of MALT1, future applications are likely to emerge.…”

Section: Malt1 Inhibitors May Be Of Therapeutic Interest For Various mentioning

confidence: 99%

See 2 more Smart Citations

Holding All the CARDs: How MALT1 Controls CARMA/CARD-Dependent Signaling

Juilland

Thome

2018

Front. Immunol.

View full text Add to dashboard Cite

The scaffold proteins CARMA1-3 (encoded by the genes CARD11, -14 and -10) and CARD9 play major roles in signaling downstream of receptors with immunoreceptor tyrosine activation motifs (ITAMs), G-protein coupled receptors (GPCR) and receptor tyrosine kinases (RTK). These receptors trigger the formation of oligomeric CARMA/CARD-BCL10-MALT1 (CBM) complexes via kinases of the PKC family. The CBM in turn regulates gene expression by the activation of NF-κB and AP-1 transcription factors and controls transcript stability. The paracaspase MALT1 is the only CBM component having an enzymatic (proteolytic) activity and has therefore recently gained attention as a potential drug target. Here we review recent advances in the understanding of the molecular function of the protease MALT1 and summarize how MALT1 scaffold and protease function contribute to the transmission of CBM signals. Finally, we will highlight how dysregulation of MALT1 function can cause pathologies such as immunodeficiency, autoimmunity, psoriasis, and cancer.

show abstract

Section: Malt1 Deregulation Is Associated With Allergy Inflammatory mentioning

confidence: 99%

Section: Malt1 Deregulation Is Associated With Allergy Inflammatory mentioning

confidence: 99%

Section: Malt1 Inhibitors May Be Of Therapeutic Interest For Various mentioning

confidence: 99%

See 1 more Smart Citation

Holding All the CARDs: How MALT1 Controls CARMA/CARD-Dependent Signaling

Juilland

Thome

2018

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…CARD14 encodes a member of the membrane‐associated guanylate kinase family, and falls within PSORS2 , the psoriasis susceptibility 2 locus . CARD14 is known to activate NF‐κB, while increasing the expression of inflammatory factors including tumor necrosis factor alpha (TNFα), interleukin‐17 (IL‐17), chemokine ligand 8 (CXCL‐8), and interleukin‐36γ (IL‐36γ) . These are canonical pathways implicated in psoriasis.…”

Section: Introductionmentioning

confidence: 99%

Histopathologic findings characteristic of CARD14‐associated papulosquamous eruption

et al. 2019

View full text Add to dashboard Cite

Background: Pathogenic mutations in caspase recruitment domain-containing protein 14 (CARD14) lead to CARD14-associated papulosquamous eruption, which shares clinicopathologic findings with psoriasis and pityriasis rubra pilaris. We aimed to describe distinguishing histopathologic features of CARD14-associated papulosquamous eruption.Methods: This retrospective study examined the histopathologic features of specimens from patients with confirmed CARD14-associated papulosquamous eruption and adult patients with plaque psoriasis and pityriasis rubra pilaris.Results: Lesional skin biopsies from patients with CARD14-associated papulosquamous eruption consistently showed alternating checkerboard parakeratosis and orthokeratosis, acanthosis without acantholysis, and dilated vessels in the dermal papillae, with some cases also showing follicular plugging.Conclusion: CARD14-associated papulosquamous eruption has a range of findings, with a predominance of features typically associated with pityriasis rubra pilaris. K E Y W O R D SCARD14, papulosquamous, pityriasis rubra pilaris, psoriasis, PSORS2

show abstract

“…IB, immunoblot; WT, wild type. of affecting T-cell and keratinocyte function (downstream of CARD11 and CARD14, respectively) (Van Nuffel et al, 2017). Targeting CARD14 directly, however, may permit the development of more specific therapies with decreased adverse effect profiles, and this merits further investigation into understanding CARD14 biology.…”

Section: Discussionmentioning

confidence: 99%

993 CARD14 gain-of-function mutation alone is sufficient to drive IL-23/IL-17-mediated psoriasiform skin inflammation in vivo

Mellett

Meier

Mohanan

et al. 2018

Journal of Investigative Dermatology

View full text Add to dashboard Cite

Rare autosomal dominant mutations in the gene encoding the keratinocyte signaling molecule CARD14, have been associated with an increased susceptibility to psoriasis, but the physiological impact of CARD14 gain-offunction mutations remains to be fully determined in vivo. Here, we report that heterozygous mice harboring a CARD14 gain-of-function mutation (Card14DE138) spontaneously develop a chronic psoriatic phenotype with characteristic scaling skin lesions, epidermal thickening, keratinocyte hyperproliferation, hyperkeratosis, and immune cell infiltration. Affected skin of these mice is characterized by elevated expression of anti-microbial peptides, chemokines, and cytokines (including T helper type 17 cell-signature cytokines) and an immune infiltrate rich in neutrophils, myeloid cells, and T cells, reminiscent of human psoriatic skin. Disease pathogenesis was driven by the IL-23/IL-17 axis, and neutralization of IL-23p19, the key cytokine in maintaining T helper type 17 cell polarization, significantly reduced skin lesions and the expression of antimicrobial peptides and proinflammatory cytokines. Therefore, hyperactivation of CARD14 alone is sufficient to orchestrate the complex immunopathogenesis that drives T helper type 17-mediated psoriasis skin disease in vivo.

show abstract

CARD14-Mediated Activation of Paracaspase MALT1 in Keratinocytes: Implications for Psoriasis

Cited by 33 publications

References 69 publications

Holding All the CARDs: How MALT1 Controls CARMA/CARD-Dependent Signaling

Holding All the CARDs: How MALT1 Controls CARMA/CARD-Dependent Signaling

Histopathologic findings characteristic of CARD14‐associated papulosquamous eruption

993 CARD14 gain-of-function mutation alone is sufficient to drive IL-23/IL-17-mediated psoriasiform skin inflammation in vivo

Contact Info

Product

Resources

About