Mononuclear Phagocyte Activation Is Associated With the Immunopathology of Psoriasis

Costa, Mariana Carvalho; Paixão, Camilla S.; Viana, Débora L.; Rocha, Bruno de Oliveira; Saldanha, Maíra; Mota, Lícia Maria Henrique da; Machado, Paulo Roberto Lima; Pagliari, Carla; Oliveira, Maria de Fátima de; Arruda, Sérgio; Carvalho, Edgar M.; Carvalho, Lucas P.

doi:10.3389/fimmu.2020.00478

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Several studies have already shown that TLR activation does not or only very slightly induces type I IFN release by monocytes [ 88 , 89 , 90 , 91 ]. Although literature data suggest that activated monocytes from psoriasis patients show significantly higher NLRP3 activity than healthy controls and that also contributes to the disease pathology [ 85 , 86 , 87 ], we could not detect differences in NLRP3 activity between the two groups. It is likely that in our present experiments, we were unable to detect increased NLRP3 activity in patients’ monocytes because we used activation signals tailored to pDCs and, though monocytes express TLR7 [ 150 ] and TLR9 [ 151 , 152 , 153 ] receptors, these cells cannot be strongly stimulated through them.…”

Section: Discussioncontrasting

confidence: 81%

“…Finally, we also compared the expression of NLRP3 pathway components in the CD14+ monocyte population from psoriatic and healthy individuals, since inflammatory cytokines produced in excess by circulating monocytes also play an important pathological role in psoriasis [ 85 , 86 , 87 ]. The ability of monocytes to produce type I IFNs is much lower than that of pDCs [ 88 , 89 , 90 , 91 ], yet we still wondered whether NLRP3 activity is also hindered by type I IFNs in the monocyte fraction of psoriatic patients.…”

Section: Resultsmentioning

confidence: 99%

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Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

Bencze

Fekete²,

Pfliegler³

et al. 2022

IJMS

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Generally, a reciprocal antagonistic interaction exists between the antiviral type I interferon (IFN) and the antibacterial nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain containing 3 (NLRP3)-dependent IL-1β pathways that can significantly shape immune responses. Plasmacytoid dendritic cells (pDCs), as professional type I IFN-producing cells, are the major coordinators of antiviral immunity; however, their NLRP3-dependent IL-1β secretory pathway is poorly studied. Our aim was to determine the functional activity of the IL-1β pathway and its possible interaction with the type I IFN pathway in pDCs. We found that potent nuclear factor-kappa B (NF-κB) inducers promote higher levels of pro-IL-1β during priming compared to those activation signals, which mainly trigger interferon regulatory factor (IRF)-mediated type I IFN production. The generation of cleaved IL-1β requires certain secondary signals in pDCs and IFN-α or type I IFN-inducing viruses inhibit IL-1β production of pDCs, presumably by promoting the expression of various NLRP3 pathway inhibitors. In line with that, we detected significantly lower IL-1β production in pDCs of psoriasis patients with elevated IFN-α levels. Collectively, our results show that the NLRP3-dependent IL-1β secretory pathway is inducible in pDCs; however, it may only prevail under inflammatory conditions, in which the type I IFN pathway is not dominant.

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Section: Discussioncontrasting

confidence: 81%

Section: Resultsmentioning

confidence: 99%

Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

Bencze

Fekete²,

Pfliegler³

et al. 2022

IJMS

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“…Among these DEmRNAs, we found inflammatory mediators CXCL9 and CCL8. CXCL9 is an important chemokine involved in T cell recruitment and is up-regulated in the plasma of patients with psoriasis[ 46 , 47 ]. Increased CXCL9 expression can aggravate the progression of psoriasis[ 48 ].…”

Section: Discussionmentioning

confidence: 99%

Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis

Shu¹,

Chen²,

Kang³

et al. 2022

WJCC

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BACKGROUND Psoriasis is a chronic inflammatory skin disease, the pathogenesis of which is more complicated and often requires long-term treatment. In particular, moderate to severe psoriasis usually requires systemic treatment. Psoriasis is also associated with many diseases, such as cardiometabolic diseases, malignant tumors, infections, and mood disorders. Psoriasis can appear at any age, and lead to a substantial burden for individuals and society. At present, psoriasis is still a treatable, but incurable, disease. Previous studies have found that microRNAs (miRNAs) play an important regulatory role in the progression of various diseases. Currently, miRNAs studies in psoriasis and dermatology are relatively new. Therefore, the identification of key miRNAs in psoriasis is helpful to elucidate the molecular mechanism of psoriasis. AIM To identify key molecular markers and signaling pathways to provide potential basis for the treatment and management of psoriasis. METHODS The miRNA and mRNA data were obtained from the Gene Expression Omnibus database. Then, differentially expressed mRNAs (DEmRNAs) and differentially expressed miRNAs (DEmiRNAs) were screened out by limma R package. Subsequently, DEmRNAs were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomics functional enrichment. The “WGCNA” R package was used to analyze the co-expression network of all miRNAs. In addition, we constructed miRNA-mRNA regulatory networks based on identified hub miRNAs. Finally, in vitro validation was performed. All experimental procedures were approved by the ethics committee of Chinese PLA General Hospital (S2021-012-01). RESULTS A total of 639 DEmRNAs and 84 DEmiRNAs were identified. DEmRNAs screening criteria were adjusted P (adj. P) value < 0.01 and |logFoldChange| (|logFC|) > 1. DEmiRNAs screening criteria were adj. P value < 0.01 and |logFC| > 1.5. KEGG functional analysis demonstrated that DEmRNAs were significantly enriched in immune-related biological functions, for example, toll-like receptor signaling pathway, cytokine-cytokine receptor interaction, and chemokine signaling pathway. In weighted gene co-expression network analysis, turquoise module was the hub module. Moreover, 10 hub miRNAs were identified. Among these 10 hub miRNAs, only 8 hub miRNAs predicted the corresponding target mRNAs. 97 negatively regulated miRNA-mRNA pairs were involved in the miRNA-mRNA regulatory network, for example, hsa-miR-21-5p-claudin 8 (CLDN8), hsa-miR-30a-3p-interleukin-1B (IL-1B), and hsa-miR-181a-5p/hsa-miR-30c-2-3p-C-X-C motif chemokine ligand 9 (CXCL9). Real-time polymerase chain reaction results showed that IL-1B and CXCL9 were up-regulated and CLDN8 was down-regulated in psoriasis with statistically significant differences. CONCLUSION The identification of potential key mo...

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“…Psoriasis is a chronic and recurrent immune-mediated skin disease that often causes disfigurement and disability in patients (1,(45)(46)(47)(48). Due to the inadequate popularization of dermatology knowledge, patients with psoriasis often receive stigmatization in their work and life, negatively affecting their quality of life and even leading to mental illnesses such as anxiety and depression.…”

Section: Discussionmentioning

confidence: 99%

Stigmatization in Patients With Psoriasis: A Mini Review

et al. 2021

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Psoriasis is a chronic and recurrent immune-related skin disease that often causes disfigurement and disability. Due to the visibility of lesions in patients and inadequate understanding of dermatology knowledge in the general public, patients with psoriasis often suffer from stigma in their daily lives, which has adverse effects on their mental health, quality of life, and therapeutic responses. This review summarized the frequently used questionnaires and scales to evaluate stigmatization in patients with psoriasis, and recent advances on this topic. Feelings of Stigmatization Questionnaire, Questionnaire on Experience with Skin Complaints, and 6-item Stigmatization Scale have been commonly used. The relationship between sociodemographic characteristics, disease-related variables, psychiatric disorders, quality of life, and stigmatization in patients with psoriasis has been thoroughly investigated with these questionnaires. Managing the stigmatization in patients with psoriasis needs cooperation among policymakers, dermatologists, psychologists, psychiatrists, researchers, and patients. Further studies can concentrate more on these existing topics, as well as other topics, including predictors of perceived stigmatization, stigmatization from non-patient groups, influence of biologics on stigmatization, and methods of coping with stigmatization.

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Mononuclear Phagocyte Activation Is Associated With the Immunopathology of Psoriasis

Cited by 7 publications

References 39 publications

Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

Interactions between the NLRP3-Dependent IL-1β and the Type I Interferon Pathways in Human Plasmacytoid Dendritic Cells

Identification of potential key molecules and signaling pathways for psoriasis based on weighted gene co-expression network analysis

Stigmatization in Patients With Psoriasis: A Mini Review

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