NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis

Tervaniemi, Mari H.; Katayama, Shintaro; Skoog, Tiina; Siitonen, H. Annika; Vuola, Jyrki; Nuutila, Kristo; Sormunen, Raija; Johnsson, Anna; Linnarsson, Sten; Suomela, Sari; Kankuri, Esko; Kere, Juha; Elomaa, Outi

doi:10.1038/srep22745

Cited by 69 publications

(81 citation statements)

References 48 publications

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“…(12,13) Card6 also shares structural features with the interferon-inducible guanosine triphosphatase (GTPase) family and can be induced by interferon in bone marrow-derived macrophages, B cells, T cells, and splenocytes. (14) Other studies also implicate Card6 involvement in immune diseases and cancers, including psoriasis (15) and gastric, colorectal, and esophageal cancers. (16) Unexpectedly, Card6-deficient mice do not exhibit any abnormalities in the innate immune response.…”

Section: And Yi-da Tangmentioning

confidence: 99%

Caspase Recruitment Domain Protein 6 Protects Against Hepatic Steatosis and Insulin Resistance by Suppressing Apoptosis Signal–Regulating Kinase 1

Sun

Zeng²,

Cheng

et al. 2018

Hepatology

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The rapidly increasing prevalence of metabolic disorders associated with nonalcoholic fatty liver disease (NAFLD) warrants further study of the underlying mechanisms to identify key regulators as targets for the development of therapeutic interventions. Caspase recruitment domain protein 6 (Card6), as a member of the CARD family that regulates cell death and immunity, may potentially control this process. Indeed, Card6 down-regulation was found to be closely associated with the fatty livers observed in NAFLD patients, obese mice, and a palmitate-treated hepatocyte model. Gain-of-function and loss-of-function Card6 mouse models demonstrated that Card6 protected mice from insulin resistance, hepatic steatosis, and inflammatory responses upon high-fat diet administration. Mechanistically, Card6 interacted with and inhibited apoptosis signal-regulating kinase 1 (Ask1) and its subsequent downstream c-Jun N-terminal kinase/p38 signaling. Furthermore, Ask1 was sufficient to mediate Card6 function, and the interaction between Ask1 and Card6 was absolutely required for Card6 function in vivo. Adenovirus-mediated Card6 overexpression in the liver effectively ameliorated insulin resistance and hepatic steatosis in ob/ob mice. Therefore, we identified Card6 as an important negative regulator in NAFLD. Conclusion: Targeting Ask1 by Card6 may be a good strategy to develop a therapeutic method against NAFLD.

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Section: And Yi-da Tangmentioning

confidence: 99%

Caspase Recruitment Domain Protein 6 Protects Against Hepatic Steatosis and Insulin Resistance by Suppressing Apoptosis Signal–Regulating Kinase 1

Sun

Zeng²,

Cheng

et al. 2018

Hepatology

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show abstract

“…Genome-wide association studies suggest a link between NLRP10 and allergic and inflammatory pathways in atopic dermatitis, food allergies, and contact hypersensitivity. Most recently, NLRP10 was found upregulated in psoriasis, which is an immune-mediated genetic disease manifested in the skin and joints and shown to contribute to delayed-type hypersensitivity response in a mouse model of atopic dermatitis (24)(25)(26)(27).…”

mentioning

confidence: 99%

NLRP10 Affects the Stability of Abin-1 To Control Inflammatory Responses

Mirza

Sowa

Lautz

et al. 2019

The Journal of Immunology

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NOD-like receptors (NLR) are critical regulators of innate immune signaling. The NLR family consists of 22 human proteins with a conserved structure containing a central oligomerization NACHT domain, an N-terminal interaction domain, and a variable number of C-terminal leucine-rich repeats. Most NLR proteins function as cytosolic pattern recognition receptors with activation of downstream inflammasome signaling, NF-κB, or MAPK activation. Although NLRP10 is the only NLR protein lacking the leucine rich repeats, it has been implicated in multiple immune pathways, including the regulation of inflammatory responses toward Leishmania major and Shigella flexneri infection. In this study, we identify Abin-1, a negative regulator of NF-κB, as an interaction partner of NLRP10 that binds to the NACHT domain of NLRP10. Using S. flexneri as an infection model in human epithelial cells, our work reveals a novel function of NLRP10 in destabilizing Abin-1, resulting in enhanced proinflammatory signaling. Our data give insight into the molecular mechanism underlying the function of NLRP10 in innate immune responses.

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“…2a). Several reports demonstrated that the expression of inflammasome components including AIM2, NOD2 and PYCARD was upregulated in psoriasis; 5,6 however, high expression of the NLRC4 gene in psoriatic lesions has never been reported. Our LC-MS/MS analysis did not detect the previously reported inflammasomes related to psoriasis probably because our sampling and analysis methods differed from those used in the previous studies.…”

Section: Discussionmentioning

confidence: 99%

Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients

Hiruma

Harada

Motoyama

et al. 2018

The Journal of Dermatology

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Inflammasomes are multimolecular complexes that control the inflammatory response. The function of inflammasomes in the pathogenesis of psoriasis is still unclear. To clarify the relationship between inflammasomes and the pathophysiology of psoriasis, and in particular, to identify molecules interacting with caspase-1, a crucial component of inflammasomes, scale extracts obtained from patients with psoriasis were immunoprecipitated with anti-caspase-1 antibody and analyzed by liquid chromatography coupled with electrospray tandem mass spectrometry (LC-MS/MS). The expression of the inflammasome component was assessed by immunohistochemical analysis and an in vitro assay. We identified several candidates for caspase-1-interacting proteins from the psoriatic scale extracts by immunoprecipitation and LC-MS/MS. Nucleotide-binding oligomerization domain-containing protein-like receptor family CARD domain-containing protein 4 (NLRC4) was the only inflammasome component among the candidates; thus, the protein is considered to be a key factor of inflammasomes in psoriasis. No inflammasome component was found in the extracts of atopic dermatitis or normal skin by LC-MS/MS. Immunohistochemical analysis demonstrated upregulation of NLRC4 in the lesional epidermis of some psoriatic patients whereas weak expression of NLRC4 was detected in the normal and non-lesional epidermis. The mRNA expression of the NLRC4 gene increased in keratinocytes at confluency, 48 h after air exposure and after the addition of 1.5 mmol/L calcium chloride. Our findings suggest that NLRC4 may be involved in the exacerbation or modification of psoriatic lesions.

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NOD-like receptor signaling and inflammasome-related pathways are highlighted in psoriatic epidermis

Cited by 69 publications

References 48 publications

Caspase Recruitment Domain Protein 6 Protects Against Hepatic Steatosis and Insulin Resistance by Suppressing Apoptosis Signal–Regulating Kinase 1

Caspase Recruitment Domain Protein 6 Protects Against Hepatic Steatosis and Insulin Resistance by Suppressing Apoptosis Signal–Regulating Kinase 1

NLRP10 Affects the Stability of Abin-1 To Control Inflammatory Responses

Key component of inflammasome, NLRC4, was identified in the lesional epidermis of psoriatic patients

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