Advances in the pathogenesis of psoriasis: from keratinocyte perspective

Cell Death and Disease, Journal Year: 2022, Volume and Issue: 13(1)

Published: Jan. 24, 2022

Abstract Psoriasis is a complex long-lasting inflammatory skin disease with high prevalence and associated comorbidity. It characterized by epidermal hyperplasia dermal infiltration of immune cells. Here, we review the role keratinocytes in pathogenesis psoriasis, focusing on factors relevant to genetics, cytokines receptors, metabolism, cell signaling, transcription factors, non-coding RNAs, antimicrobial peptides, proteins other different functions. The critical initiating maintaining state suggests great significance targeting for treatment psoriasis.

Language: Английский

---

Cytokinocytes: the diverse contribution of keratinocytes to immune responses in skin

JCI Insight, Journal Year: 2020, Volume and Issue: 5(20)

Published: Oct. 14, 2020

The skin serves as the primary interface between our body and external environment acts a barrier against entry of physical agents, chemicals, microbes. Keratinocytes make up main cellular constitute outermost layer skin, contributing to formation epidermis, they are crucial for maintaining integrity this barrier. Beyond serving component, keratinocytes actively participate in tissue homeostasis, shaping, amplifying, regulating immune responses skin. act sentinels, continuously monitoring changes environment, and, through microbial sensing, stretch, or other stimuli, can initiate broad range inflammatory via secretion various cytokines, chemokines, growth factors. This diverse function contributes highly variable clinical manifestation responses. In Review, we highlight functions epidermal their contribution immune-mediated diseases.

Language: Английский

---

Inhibition of keratinocyte ferroptosis suppresses psoriatic inflammation

Cell Death and Disease, Journal Year: 2021, Volume and Issue: 12(11)

Published: Oct. 27, 2021

Abstract Psoriasis is a common, chronic, and recurrent inflammatory disease. It characterized by hyperproliferation abnormal differentiation of keratinocytes. Keratinocyte death also involved in many pathophysiological conditions amplifies the cascade. As newly recognized form cell death, ferroptosis several diseases. In this study, we aimed to investigate previously unrecognized role for psoriasis. Ferroptosis mediated lipid peroxidation iron overload. Compared with normal lesions, mRNA expression acyl-CoA synthetase long-chain family member 4 ( ACSL4 ), prostaglandin-endoperoxide synthase 2 PTGS2 transferrin receptor TFRC ) were highly expressed psoriatic decreased levels glutathione peroxidase GPX4 ferritin light chain FTL heavy 1 FTH1 ). The protein consistent their levels. A similar tendency was observed erastin-treated human primary keratinocytes Imiquimod (IMQ)-induced model To correlation between inflammation peroxidation, analyzed single-cell RNA-sequencing data identified 15 types. There high activity oxidation Th22/Th17 response at level. Moreover, ferrostatin-1 (Fer-1), potent inhibitor suppressed ferroptosis-related changes alleviated psoriasiform dermatitis IMQ-induced models. Additionally, Fer-1 blocked responses vitro vivo, reducing production cytokines including TNF-α , IL-6 IL-1α IL-1β IL-17 IL-22 IL-23 . This study revealed an pattern which specific molecules enhance reactions

Language: Английский

---

Skin Barrier Dysregulation in Psoriasis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(19), P. 10841 - 10841

Published: Oct. 7, 2021

The skin barrier is broadly composed of two elements-a physical mostly localised in the epidermis, and an immune both dermis epidermis. These systems interact cooperatively to maintain homeostasis overall human health. However, if dysregulated, several diseases may arise. Psoriasis one most prevalent associated with disrupted function. It characterised by formation psoriatic lesions, aberrant differentiation proliferation keratinocytes, excessive inflammation. In this review, we summarize recent discoveries disease pathogenesis, including contribution cells, genetic environmental factors, how they advance current future treatments.

Language: Английский

---

Signaling pathways and targeted therapies for psoriasis

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Nov. 27, 2023

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with high burden on individuals, health systems, society worldwide. With the immunological pathologies pathogenesis of psoriasis becoming gradually revealed, therapeutic approaches for this have gained revolutionary progress. Nevertheless, mechanisms less common forms remain elusive. Furthermore, severe adverse effects recurrence upon treatment cessation should be noted addressed during treatment, which, however, has been rarely explored integration preliminary findings. Therefore, it crucial to comprehensive understanding behind pathogenesis, which might offer new insights research lead more substantive progress in expand clinical options treatment. In review, we looked briefly introduce epidemiology, subtypes, pathophysiology, comorbidities systematically discuss signaling pathways involving extracellular cytokines intracellular transmission, as well cross-talk between them. discussion, also paid attention potential metabolic epigenetic molecular mechanistic cascades related its comorbidities. This review outlined current psoriasis, especially targeted therapies novel strategies, mechanism recurrence.

Language: Английский

---

Pathophysiology of psoriasis: A review

The Journal of Dermatology, Journal Year: 2021, Volume and Issue: 48(6), P. 722 - 731

Published: April 22, 2021

Abstract Psoriasis is a complex chronic inflammatory skin disease caused by the dynamic interplay between multiple genetic risk foci, environmental factors, and excessive immunological abnormalities. affects approximately 2% of population worldwide, dramatic advances have been achieved in understanding treatment options for psoriasis. Recent progress biological therapies has revealed fundamental roles tumor necrosis factor‐α, interleukin (IL)‐23p19, IL‐17A axis together with skin‐resident immune cells major signal transduction pathways pathogenesis In addition to IL‐17‐producing T helper17 cells, innate lymphoid cell (ILC)3 induces psoriasis rashes directly without T‐cell/antigen interaction response released antimicrobial peptides from activated keratinocytes cytokines. ILC3 typically expresses retinoic acid receptor‐related orphan receptor gamma t nucleus, matures presence IL‐7 IL‐23, produces IL‐17 IL‐22. The number ILC3s increased blood, rash, even nonrash areas psoriatic skin. significantly associated cardiovascular disease, metabolic syndrome, disorders, particularly severe type. similarity enterobacteria gut that diabetic patients may be related its pathogenesis. current review, we focus on pathophysiology accelerated loop, danger keratinocytes, cytokines, IL‐23p19. addition, pathophysiological speculation regard morphology supplemented. Finally, differences similarities atopic dermatitis are discussed.

Language: Английский

---

Current Concepts of Psoriasis Immunopathogenesis

International Journal of Molecular Sciences, Journal Year: 2021, Volume and Issue: 22(21), P. 11574 - 11574

Published: Oct. 26, 2021

Psoriasis is a recurrent, chronic, immune-mediated, systemic inflammatory disease of the skin, joints, and other organic systems. After atopic dermatitis, chronic stationary psoriasis most common skin disease, affecting an average 2-4% world's population. The carries significant burden due to its numerous comorbidities major impact on patients' social emotional aspects life. According current knowledge, multifactorial that occurs in genetically predisposed individuals under various environmental factors, which trigger immune response disorder with series complex cascades. initiated maintained by mutual interaction innate adaptive cells, primarily dendritic T lymphocytes, keratinocytes, whose leading role alternates at different stages consisting mainly IL-23/Th17 pathway. Inflammatory events result consequent epidermal dermal changes evolution characteristic psoriatic phenotype, respectively. This paper aims present comprehensive overview knowledge genetic etiological immunopathogenesis, cellular cytokine participants pathways this disease.

Language: Английский

---

Reactive Oxygen Species-Responsive Gel-Based Microneedle Patches for Prolonged and Intelligent Psoriasis Management

ACS Nano, Journal Year: 2023, Volume and Issue: 17(5), P. 4346 - 4357

Published: Feb. 27, 2023

Psoriasis is an inflammatory skin disease. Microneedle (MN) patches can improve psoriasis treatment outcomes by increasing local drug content in the skin. As frequently relapses, developing intelligent MN-based delivery systems with prolonged therapeutic levels and improved efficiency of great significance. Here, we designed detachable H2O2-responsive gel-based MN containing methotrexate (MTX) epigallocatechin gallate (EGCG) using EGCG as both cross-linkers for needle-composited materials anti-inflammatory drugs. The MNs had dual-mode release kinetics, which quickly released MTX diffusively sustainably way. Compared dissolving MNs, extended retention EGCG, leading to reactive oxygen species (ROS) scavenging effects. ROS-responsive that transdermally delivered antiproliferative drugs psoriasis-like prophylactic animal models.

Language: Английский

---

Early disease intervention with guselkumab in psoriasis leads to a higher rate of stable complete skin clearance (‘clinical super response’): Week 28 results from the ongoing phase IIIb randomized, double‐blind, parallel‐group, GUIDE study

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2023, Volume and Issue: 37(10), P. 2016 - 2027

Published: June 1, 2023

Guselkumab is an interleukin (IL)-23 inhibitor with demonstrated efficacy in patients psoriasis.Evaluate the impact of early disease intervention on clinical responses following 28 weeks guselkumab treatment moderate-to-severe plaque psoriasis. Correlate response and duration data serum biomarker data.GUIDE a phase IIIb randomized, double-blind, parallel-group, multicentre study adults In part 1, short (SDD [≤2 years]) or long (LDD [>2 received 100 mg at Week (W) 0, 4, 12, 20. Those achieving complete skin clearance W20 W28 were defined as super responder (SRe). A multivariable logistic regression analysed association between baseline factors likelihood becoming SRe. The relationship response, was assessed W0 4.In total, 880 enrolled (SDD/LDD = 40.6%/59.4% patients). More SDD than LDD achieved absolute Psoriasis Area Severity Index (PASI) 0 (51.8% vs. 39.4%) SRes (43.7% 28.1% [overall 34.4%]). also PASI quicker (median 141 200 days). Disease prior biologic use had greatest SRe, no strong among these independent variables. At baseline, there significant differences levels IL-17A, IL-17F, IL-22 β-defensin 2 patients, SRe non-SRe patients. rapidly decreased markers systemic inflammation across all patient groups W4. well tolerated.Guselkumab consistent subpopulations, systemically. proportion higher indicating may improve outcomes.

Language: Английский

---

Regulation of Skin Barrier Function via Competition between AHR Axis versus IL-13/IL-4‒JAK‒STAT6/STAT3 Axis: Pathogenic and Therapeutic Implications in Atopic Dermatitis

Journal of Clinical Medicine, Journal Year: 2020, Volume and Issue: 9(11), P. 3741 - 3741

Published: Nov. 20, 2020

Atopic dermatitis (AD) is characterized by skin inflammation, barrier dysfunction, and chronic pruritus. As the anti-interleukin-4 (IL-4) receptor α antibody dupilumab improves all three cardinal features of AD, type 2 cytokines IL-4 especially IL-13 have been indicated to pathogenic significance in AD. Accumulating evidence has shown that function regulated via competition between aryl hydrocarbon (AHR) axis (up-regulation barrier) IL-13/IL-4‒JAK‒STAT6/STAT3 (down-regulation barrier). This latter also induces oxidative stress, which exacerbates inflammation. Conventional recently developed agents for treating AD such as steroid, calcineurin inhibitors, cyclosporine, dupilumab, JAK inhibitors inhibit axis, while older remedies coal tar glyteer are antioxidative AHR agonists. In this article, I summarize therapeutic implications

Language: Английский

---