Genetic variations of<i>NLRP1</i>: susceptibility in psoriasis

Ekman, Anna-Karin; Verma, Deepti; Fredrikson, Mats; Bivik, Cecilia; Enerbäck, Charlotta

doi:10.1111/bjd.13178

Cited by 66 publications

(60 citation statements)

References 19 publications

(35 reference statements)

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“…Despite strikingly similar clinical aspects of the skin and the corneal dyskeratosis and dental problems for patient 3, the patients we describe presented a more complex phenotype characterised by a unique combination of features, namely recurrent fever with elevated biological markers of inflammation, arthritis initially classified as sJIA in family 1, intraepithelial dyskeratosis, vitamin A deficiency, slight autoimmunity and high transitional B-cell count in two of the three patients. The similar dermatological manifestations between our patients and those described by Soler et al ,23 as well as the genetic susceptibility of NLRP1 in skin disorders such as vitiligo10 and psoriasis,24 suggest that NLRP1 may have a unknown role in skin innate immune responses.…”

Section: Discussionsupporting

confidence: 87%

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis)

et al. 2016

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Section: Discussionsupporting

confidence: 87%

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis)

et al. 2016

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“…Increasing evidence connects the NLRP1 inflammasome to the pathogenesis of skin-associated autoimmune diseases, such as vitiligo, lupus erythematosus, pemphigus vulgaris, and psoriasis [15, 17, 20, 45]. Compared to other inflammasome complexes, such as NLPR3 and AIM2 expressed in keratinocytes, NLRP1 can activate caspase-5 besides inflammasome ubiquitous caspase-1 [8, 11].…”

Section: Discussionmentioning

confidence: 99%

Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation

et al. 2017

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IL-1β is a potent player in cutaneous inflammation and central for the development of a Th17 micro-milieu in autoinflammatory diseases including psoriasis. Its production is controlled at the transcriptional level and by subsequent posttranslational processing via inflammatory caspases. In this study, we detected inflammatory caspase-5 active in epidermal keratinocytes and in psoriatic skin lesions. Further, interferon-γ and interleukin-17A synergistically induced caspase-5 expression in cultured keratinocytes, which was dependent on the antimicrobial peptide psoriasin (S100A7). However, diseases-relevant triggers for caspase-5 activity and IL-1β production remain unknown. Recently, extranuclear DNA has been identified as danger-signals abundant in the psoriatic epidermis. Here, we could demonstrate that cytosolic double-stranded (ds) DNA transfected into keratinocytes triggered the activation of caspase-5 and the release of IL-1β. Further, interleukin-17A promoted caspase-5 function via facilitation of the NLRP1-inflammasome. Anti-inflammatory vitamin D interfered with the IL-1β release and suppressed caspase-5 in keratinocytes and in psoriatic skin lesions. Our data link the disease-intrinsic danger signals psoriasin (S100A7) and dsDNA for NLPR1-dependent caspase-5 activity in psoriasis providing potential therapeutic targets in Th17-mediated skin autoinflammation.

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“…Likewise, in one study about rheumatoid arthritis in Han Chinese, Sui et al [20] found that the NLRP1 (rs878329, G>C) polymorphism was a risk factor for rheumatoid arthritis. Another study performed by Ekman et al [21] showed that NLRP1 (rs878329, G>C) polymorphism correlated with psoriasis susceptibility. These results showed that rs878329 (G>C) might be a vital gene in the function of NLRP1.…”

Section: Discussionmentioning

confidence: 99%

Association between NLPR1, NLPR3, and P2X7R Gene Polymorphisms with Partial Seizures

Wang

Liao

et al. 2017

BioMed Research International

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Objectives. Clinical and experimental evidence has clarified that the inflammatory processes within the brain play a pivotal role in the pathophysiology of seizures and epilepsy. Inflammasomes and P2X7 purinergic receptor (P2X7R) are important mediators during the inflammatory process. Therefore, we investigated the possible association between partial seizures and inflammasomes NLPR1, NLRP3, and P2X7R gene polymorphisms in the present study. Method. A total of 163 patients and 201 health controls were enrolled in this study and polymorphisms of NLPR1, NLRP3, and P2X7R genes were detected using polymerase chain reaction- (PCR-) ligase detection reaction method. Result. The frequency of rs878329 (G>C) genotype with C (CG + CC) was significantly lower among patients with partial seizures relative to controls (OR = 2.033, 95% CI = 1.290–3.204, p = 0.002 for GC + CC versus GG). Intriguingly, we found that the significant difference of rs878329 (G>C) genotype and allele frequency only existed among males (OR = 2.542, 95% CI = 1.344–4.810, p = 0.004 for GC + CC versus GG), while there was no statistically significant difference among females. However, no significant results were presented for the genotype distributions of rs8079034, rs4612666, rs10754558, rs2027432, rs3751143, and rs208294 polymorphisms between patients and controls. Conclusion. Our study demonstrated the potentially significant role of NLRP1 rs878329 (G>C) in developing susceptibility to the partial seizures in a Chinese Han population.

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Genetic variations ofNLRP1: susceptibility in psoriasis

Abstract: Our data support the involvement of NLRP1 and the NLRP1 inflammasome in psoriasis susceptibility and further support the role of innate immunity in psoriasis.

Cited by 66 publications

References 19 publications

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis)

A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLRP1-associated autoinflammation with arthritis and dyskeratosis)

Th17 micro-milieu regulates NLRP1-dependent caspase-5 activity in skin autoinflammation

Association between NLPR1, NLPR3, and P2X7R Gene Polymorphisms with Partial Seizures

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