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New Insights into Psoriasis

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 47431

Special Issue Editors


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Guest Editor
1. Department of Dermatology, Venereology and Allergology, Medical University of Gdansk, 80-214 Gdansk, Poland
2. Molecular Laboratory, Invicta Fertility and Reproductive Centre, 81-740 Sopot, Poland
Interests: genetic and epigenetic changes in mastocytosis; psoriasis; atopic dermatitis; treg regulation of skin immunology; chemokines and cytokines network in skin diseases; genetic and chromosomal changes in melanomas; sarcomas; T-cell lymphomas and breast carcinomas; genetic and chromosomal causes of infertility; preimplantation, prenatal and postnatal molecular and cytogenetic diagnostic
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Guest Editor
Department of Dermatology, Sexually Transmitted Diseases and Clinical Immunology, School of Medicine, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland
Interests: psoriasis; inflammatory immune-mediated inflammatory disease; metabolic diseases
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Chair and Department of Dermatology, Venereology and Pediatric Dermatology, Medical University of Lublin, Lublin, Poland
Interests: psoriasis and comorbidities; atopic dermatitis; morphea; systemic sclerosis; skin cancers
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Gdańsk, Poland
Interests: psoriasis; psoriatic arthritis; granulomatous skin diseases; cutaneous complications of permanent pigmentation

Special Issue Information

Dear Colleagues,

Psoriasis is a common, chronic, inflammatory, immune-mediated skin disease affecting about 2% of the world's population. It is associated with many comorbidities including arthritis, metabolic syndrome and an increased cardiovascular disease risk, increasing the risk of mortality due to myocardial infarction and stroke. 

The main cause of the disease is the overactivation of the skin's innate and acquired immune system cells by external factors (trauma, drugs and infections) and internal factors (stress, self DNA/AMP, and RNA/LL37). These cells secrete cytokines, chemokines and growth factors that stimulate keratinocyte proliferation, neoangiogenesis and inflammation. The IFNγ, TNFα and IL-23/IL17 axis, which activates the NF-κB pathway, plays a dominant role in the pathogenesis of the disease.

A complex interaction between epigenetics, genetics and the inflammatory signaling networks of skin and immune cell mediators has been proved in many studies.

Psoriasis has been shown to be associated with the mutation of more than 60 genes. They include genes encoding:

  • Cytokines and their receptors, which play a role in the formation and regulation of the function of Th17/Tc17, Th22, Th1, Th2 and NK cells.
  • Proteins related to the regulation of inflammatory processes related to the activation and regulation of the functions of pathways dependent on the transcription factor NF-κB.
  • Structural proteins of the epidermis.

Regarding epigenetic mechanisms, histone modifications, promoter methylations, and long noncoding RNA and microRNA hyperexpression are considered to be additional factors contributing to psoriasis pathogenesis, as they regulate abnormal keratinocyte differentiation and proliferation, aberrant keratinocyte–inflammatory cell communication, neoangiogenesis and chronic inflammation. 

In this Special Issue, we will publish recent data regarding the pathogenesis, comorbidities and therapy of psoriasis. We invite you to submit original and review publications based on the results of molecular research.

Dr. Bogusław Nedoszytko
Prof. Dr. Agnieszka Owczarczyk-Saczonek
Prof. Dr. Dorota Krasowska
Dr. Aneta Szczerkowska-Dobosz
Guest Editors

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Keywords

  • psoriasis and psoriatic arthritis
  • IFNγ
  • TNFα
  • IL-23/IL-17 axis
  • genetic and epigenetic factors
  • metabolic risk factors
  • cardiometabolic syndromes
  • stress hormones
  • biologic therapy

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Published Papers (10 papers)

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Editorial

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3 pages, 190 KiB  
Editorial
New Insights into Psoriasis
by Boguslaw Nedoszytko, Agnieszka Owczarczyk-Saczonek, Dorota Krasowska and Aneta Szczerkowska-Dobosz
Int. J. Mol. Sci. 2022, 23(21), 12851; https://doi.org/10.3390/ijms232112851 - 25 Oct 2022
Viewed by 1320
Abstract
Psoriasis is a chronic inflammatory skin disease with many comorbidities resulting from not only local but also systemic inflammation [...] Full article
(This article belongs to the Special Issue New Insights into Psoriasis)

Research

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16 pages, 2023 KiB  
Article
Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation
by Kenta Ikeda, Shin Morizane, Takahiko Akagi, Sumie Hiramatsu-Asano, Kota Tachibana, Ayano Yahagi, Masanori Iseki, Hideaki Kaneto, Jun Wada, Katsuhiko Ishihara, Yoshitaka Morita and Tomoyuki Mukai
Int. J. Mol. Sci. 2022, 23(8), 4312; https://doi.org/10.3390/ijms23084312 - 13 Apr 2022
Cited by 23 | Viewed by 4263
Abstract
Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal [...] Read more.
Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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17 pages, 2945 KiB  
Article
The Effects of Vitamin D on the Expression of IL-33 and Its Receptor ST2 in Skin Cells; Potential Implication for Psoriasis
by Justyna M. Wierzbicka, Anna Piotrowska, Dorota Purzycka-Bohdan, Anna Olszewska, Joanna I. Nowak, Aneta Szczerkowska-Dobosz, Bogusław Nedoszytko, Roman J. Nowicki and Michał A. Żmijewski
Int. J. Mol. Sci. 2021, 22(23), 12907; https://doi.org/10.3390/ijms222312907 - 29 Nov 2021
Cited by 10 | Viewed by 2582
Abstract
Interleukin 33 (IL-33) belongs to the IL-1 family and is produced constitutively by epithelial and endothelial cells of various organs, such as the skin. It takes part in the maintenance of tissue homeostasis, repair, and immune response, including activation of Th2 lymphocytes. Its [...] Read more.
Interleukin 33 (IL-33) belongs to the IL-1 family and is produced constitutively by epithelial and endothelial cells of various organs, such as the skin. It takes part in the maintenance of tissue homeostasis, repair, and immune response, including activation of Th2 lymphocytes. Its involvement in pathogenesis of several inflammatory diseases including psoriasis was also suggested, but this is not fully understood. The aim of the study was to investigate expression of IL-33 and its receptor, ST2, in psoriasis, and the effects of the active form of vitamin D (1,25(OH)2D3) on their expression in skin cells. Here we examined mRNA and protein profiles of IL-33 and ST2 in 18 psoriatic patients and healthy volunteers by qPCR and immunostaining techniques. Potential effects of 1,25(OH)2D3 and its receptor (VDR) on the expression of IL-33 and ST2 were tested in cultured keratinocytes, melanocytes, fibroblasts, and basal cell carcinoma cells. It was shown that 1,25(OH)2D3 effectively stimulated expression of IL-33 and its receptor ST2’s mRNAs in a time-dependent manner, in keratinocytes and to the lesser extends in melanocytes, but not in fibroblasts. Furthermore, the effect of vitamin D on expression of IL-33 and ST2 was VDR-dependent. Finally, we demonstrated that the expression of mRNA for IL-33 was mainly elevated in the psoriatic skin but not in its margin. Interestingly, ST2 mRNA was downregulated in psoriatic lesion compared to both marginal tissue as well as healthy skin. Our data indicated that vitamin D can modulate IL-33 signaling, opening up new perspectives for our understanding of the mechanism of vitamin D action in psoriasis therapy. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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19 pages, 3726 KiB  
Article
Psoriasiform Inflammation Is Associated with Mitochondrial Fission/GDAP1L1 Signaling in Macrophages
by Ahmed Alalaiwe, Chi-Yuan Chen, Zi-Yu Chang, Jui-Tai Sung, Shih-Yi Chuang and Jia-You Fang
Int. J. Mol. Sci. 2021, 22(19), 10410; https://doi.org/10.3390/ijms221910410 - 27 Sep 2021
Cited by 15 | Viewed by 3592
Abstract
While psoriasis is known as a T cell- and dendritic cell-driven skin inflammation disease, macrophages are also reported to play some roles in its development. However, the signaling pathway of activated macrophages contributing to psoriasis is not entirely understood. Thus, we aimed to [...] Read more.
While psoriasis is known as a T cell- and dendritic cell-driven skin inflammation disease, macrophages are also reported to play some roles in its development. However, the signaling pathway of activated macrophages contributing to psoriasis is not entirely understood. Thus, we aimed to explore the possible mechanisms of how macrophages initiate and sustain psoriasis. The differentiated THP1 cells, stimulated by imiquimod (IMQ), were utilized as the activated macrophage model. IMQ was also employed to produce psoriasis-like lesions in mice. A transcriptomic assay of macrophages revealed that the expressions of pro-inflammatory mediators and GDAP1L1 were largely increased after an IMQ intervention. The depletion of GDAP1L1 by short hairpin (sh)RNA could inhibit cytokine release by macrophages. GDAP1L1 modulated cytokine production by activating the phosphorylation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways. Besides GDAP1L1, another mitochondrial fission factor, Drp1, translocated from the cytosol to mitochondria after IMQ stimulation, followed by the mitochondrial fragmentation according to the immunofluorescence imaging. Clodronate liposomes were injected into the mice to deplete native macrophages for examining the latter’s capacity on IMQ-induced inflammation. The THP1 cells, with or without GDAP1L1 silencing, were then transplanted into the mice to monitor the deposition of macrophages. We found a significant THP1 accumulation in the skin and lymph nodes. The silencing of GDAP1L1 in IMQ-treated animals reduced the psoriasiform severity score from 8 to 2. After depleting GDAP1L1, the THP1 recruitment in the lymph nodes was decreased by 3-fold. The skin histology showed that the GDAP1L1-mediated macrophage activation induced neutrophil chemotaxis and keratinocyte hyperproliferation. Thus, mitochondrial fission can be a target for fighting against psoriatic inflammation. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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Review

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23 pages, 1598 KiB  
Review
Vitamin D Signaling in Psoriasis: Pathogenesis and Therapy
by Anna A. Brożyna, Radomir M. Slominski, Bogusław Nedoszytko, Michal A. Zmijewski and Andrzej T. Slominski
Int. J. Mol. Sci. 2022, 23(15), 8575; https://doi.org/10.3390/ijms23158575 - 2 Aug 2022
Cited by 27 | Viewed by 7011
Abstract
Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2–3% of the world’s population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. [...] Read more.
Psoriasis is a systemic, chronic, immune-mediated disease that affects approximately 2–3% of the world’s population. The etiology and pathophysiology of psoriasis are still unknown, but the activation of the adaptive immune system with the main role of T-cells is key in psoriasis pathogenesis. The modulation of the local neuroendocrine system with the downregulation of pro-inflammatory and the upregulation of anti-inflammatory messengers represent a promising adjuvant treatment in psoriasis therapies. Vitamin D receptors and vitamin D-mediated signaling pathways function in the skin and are essential in maintaining the skin homeostasis. The active forms of vitamin D act as powerful immunomodulators of clinical response in psoriatic patients and represent the effective and safe adjuvant treatments for psoriasis, even when high doses of vitamin D are administered. The phototherapy of psoriasis, especially UVB-based, changes the serum level of 25(OH)D, but the correlation of 25(OH)D changes and psoriasis improvement need more clinical trials, since contradictory data have been published. Vitamin D derivatives can improve the efficacy of psoriasis phototherapy without inducing adverse side effects. The anti-psoriatic treatment could include non-calcemic CYP11A1-derived vitamin D hydroxyderivatives that would act on the VDR or as inverse agonists on RORs or activate alternative nuclear receptors including AhR and LXRs. In conclusion, vitamin D signaling can play an important role in the natural history of psoriasis. Selective targeting of proper nuclear receptors could represent potential treatment options in psoriasis. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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21 pages, 1233 KiB  
Review
Killing Two Birds with One Stone: Potential Therapies Targeting Psoriasis and Atherosclerosis at the Same Time
by Eva Klara Merzel Šabović, Mateja Starbek Zorko and Miodrag Janić
Int. J. Mol. Sci. 2022, 23(12), 6648; https://doi.org/10.3390/ijms23126648 - 14 Jun 2022
Cited by 4 | Viewed by 2939
Abstract
Psoriasis is a chronic systemic inflammatory disease. Due to systemic inflammation, it is associated with many comorbidities. Among them, cardiovascular diseases represent the most common causes of morbidity and mortality in this population. Therefore, physicians treating patients with psoriasis should keep in mind [...] Read more.
Psoriasis is a chronic systemic inflammatory disease. Due to systemic inflammation, it is associated with many comorbidities. Among them, cardiovascular diseases represent the most common causes of morbidity and mortality in this population. Therefore, physicians treating patients with psoriasis should keep in mind that, as important as the treatment of psoriasis, awareness of cardiovascular risk deserves additional attention. Thus, in parallel with psoriasis treatment, a cardiovascular risk assessment must also be performed and addressed accordingly. In addition to encouraging non-pharmacologic strategies for a healthy lifestyle, physicians should be familiar with different pharmacologic options that can target psoriasis and reduce cardiovascular risk. In the present article, we present the pathophysiological mechanisms of the psoriasis and cardiometabolic interplay, our view on the interaction of psoriasis and cardiovascular disease, review the atherosclerotic effect of therapeutic options used in psoriasis, and vice versa, i.e., what the effect of medications used in the prevention of atherosclerosis could be on psoriasis. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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10 pages, 730 KiB  
Review
The Role of the Neutrophilic Network in the Pathogenesis of Psoriasis
by Joanna Czerwińska and Agnieszka Owczarczyk-Saczonek
Int. J. Mol. Sci. 2022, 23(3), 1840; https://doi.org/10.3390/ijms23031840 - 6 Feb 2022
Cited by 14 | Viewed by 3558
Abstract
One role of neutrophils, the most abundant innate immune sentinels, is neutrophil extracellular trap (NET) formation, which plays a significant role in immune surveillance. However, NET operation is bidirectional. Recent studies report that NETs may contribute to the development of autoimmune diseases such [...] Read more.
One role of neutrophils, the most abundant innate immune sentinels, is neutrophil extracellular trap (NET) formation, which plays a significant role in immune surveillance. However, NET operation is bidirectional. Recent studies report that NETs may contribute to the development of autoimmune diseases such as psoriasis. The participation of neutrophils in the pathogenesis of that disease is dependent on an autoinflammatory feedback loop between neutrophils, lymphocytes, dendritic cells and keratinocytes. Our aim was to clarify the field of NET research in psoriasis and highlight the main factors required for NET generation, which may be a target of new therapies. This article presents a comphrehensive review concerning studies addressing the participation of neutrophils in the pathogenesis of psoriasis. Based on the available English-language literature, we discuss original papers presenting significant research findings which may help to understand and interpret the NET formation process in psoriasis, as well as the newest systematic reviews on PubMed. Next, the comparison, synthesis and summary of reported results were performed to clearly indicate the specific component of the NET which participates in the development of psoriasis. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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15 pages, 712 KiB  
Review
The Brain–Skin Axis in Psoriasis—Psychological, Psychiatric, Hormonal, and Dermatological Aspects
by Luiza Marek-Jozefowicz, Rafał Czajkowski, Alina Borkowska, Bogusław Nedoszytko, Michał A. Żmijewski, Wiesław J. Cubała and Andrzej T. Slominski
Int. J. Mol. Sci. 2022, 23(2), 669; https://doi.org/10.3390/ijms23020669 - 8 Jan 2022
Cited by 51 | Viewed by 11854
Abstract
Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play [...] Read more.
Psoriasis is a chronic inflammatory skin disease with systemic manifestation, in which psychological factors play an important role. The etiology of psoriasis is complex and multifactorial, including genetic background and environmental factors such as emotional or physical stress. Psychological stress may also play a role in exacerbation of psoriasis, by dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis, sympathetic–adrenal–medullary axis, peripheral nervous system, and immune system. Skin cells also express various neuropeptides and hormones in response to stress, including the fully functional analog of the HPA axis. The deterioration of psoriatic lesions is accompanied by increased production of inflammatory mediators, which could contribute to the imbalance of neurotransmitters and the development of symptoms of depression and anxiety. Therefore, deregulation of the crosstalk between endocrine, paracrine, and autocrine stress signaling pathways contributes to clinical manifestations of psoriasis, which requires multidisciplinary approaches. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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17 pages, 332 KiB  
Review
Analysis of the Potential Genetic Links between Psoriasis and Cardiovascular Risk Factors
by Dorota Purzycka-Bohdan, Anna Kisielnicka, Michał Bohdan, Aneta Szczerkowska-Dobosz, Marta Sobalska-Kwapis, Bogusław Nedoszytko and Roman J. Nowicki
Int. J. Mol. Sci. 2021, 22(16), 9063; https://doi.org/10.3390/ijms22169063 - 23 Aug 2021
Cited by 16 | Viewed by 3815
Abstract
Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general [...] Read more.
Cardiovascular risk factors are one of the most common comorbidities in psoriasis. A higher prevalence of hypertension, insulin resistance and type 2 diabetes, dyslipidemia, obesity, metabolic syndrome, depression, as well as cardiovascular disease was confirmed in psoriatic patients in comparison to the general population. Data suggest that psoriasis and systemic inflammatory disorders may originate from the pleiotropic interactions with many genetic pathways. In this review, the authors present the current state of knowledge on the potential genetic links between psoriasis and cardiovascular risk factors. The understanding of the processes linking psoriasis with cardiovascular risk factors can lead to improvement of psoriasis management in the future. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
11 pages, 3390 KiB  
Review
Aberrations in Lipid Expression and Metabolism in Psoriasis
by Julia Nowowiejska, Anna Baran and Iwona Flisiak
Int. J. Mol. Sci. 2021, 22(12), 6561; https://doi.org/10.3390/ijms22126561 - 18 Jun 2021
Cited by 54 | Viewed by 3944
Abstract
Psoriasis (PSO) is a common skin disease that affects about 1%–3% of the general population. It is a great medical, social and economic burden since PSO is associated with many comorbidities, of which the most common are cardiometabolic disorders. Psoriatic patients suffer more [...] Read more.
Psoriasis (PSO) is a common skin disease that affects about 1%–3% of the general population. It is a great medical, social and economic burden since PSO is associated with many comorbidities, of which the most common are cardiometabolic disorders. Psoriatic patients suffer more frequently from obesity, dyslipidemia, atherosclerosis, and nonalcoholic fatty liver disease. Research shows that lipid expression and metabolism disorders are present more often in such patients. This review focuses on a variety of aberrations in lipids in the skin, blood, and adipose tissue in psoriatic patients and their multifactorial impact on the pathogenesis of psoriasis. Full article
(This article belongs to the Special Issue New Insights into Psoriasis)
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