Skin Barrier Function: The Interplay of Physical, Chemical, and Immunologic Properties

Cells, Journal Year: 2023, Volume and Issue: 12(23), P. 2745 - 2745

Published: Nov. 30, 2023

An intact barrier function of the skin is important in maintaining health. The regulation depends on a multitude molecular and immunological signaling pathways. By examining healthy barrier, including maintenance acid mantle appropriate levels ceramides, dermatologists can better formulate solutions to address issues that are related disrupted barrier. Conversely, by understanding specific disruptions associated with conditions, such as atopic dermatitis or psoriasis, development new compounds could target pathways provide more effective relief for patients. We aim review key factors mediating inflammation, acidity, interleukins, nuclear factor kappa B, sirtuin 3. Furthermore, we will discuss current emerging treatment options conditions.

Language: Английский

---

IL-17D-induced inhibition of DDX5 expression in keratinocytes amplifies IL-36R-mediated skin inflammation

Nature Immunology, Journal Year: 2022, Volume and Issue: 23(11), P. 1577 - 1587

Published: Oct. 21, 2022

Abstract Aberrant RNA splicing in keratinocytes drives inflammatory skin disorders. In the present study, we found that helicase DDX5 was downregulated from lesions patients with atopic dermatitis and psoriasis, mice keratinocyte-specific deletion of Ddx5 ( ∆KC ) were more susceptible to cutaneous inflammation. Inhibition expression induced by cytokine interleukin (IL)-17D through activation CD93–p38 MAPK–AKT–SMAD2/3 signaling pathway led pre-messenger events favored production membrane-bound, intact IL-36 receptor (IL-36R) at expense soluble IL-36R (sIL-36R) selective amplification IL-36R-mediated responses Restoration sIL-36R experimental or psoriasis suppressed inflammation alleviated disease phenotypes. These findings indicate IL-17D modulation controls during diseases.

Language: Английский

---

IL-1 Family Cytokines in Inflammatory Dermatoses: Pathogenetic Role and Potential Therapeutic Implications

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(16), P. 9479 - 9479

Published: Aug. 22, 2022

The interleukin-1 (IL-1) family is involved in the correct functioning and regulation of innate immune system, linking adaptative responses. This complex composed by several cytokines, receptors, co-receptors, all working a balanced way to maintain homeostasis. Dysregulation these processes results tissue inflammation pathogenesis common inflammatory dermatoses such as psoriasis, hidradenitis suppurativa, atopic dermatitis. Therefore, therapeutic targeting IL-1 pathways has been studied, monoclonal antibodies are currently being assessed clinical trials. So far, promising have obtained with anti-IL-36R spesolimab imsidolimab pustular their efficacy tested other conditions.

Language: Английский

---

Current management of generalized pustular psoriasis

Experimental Dermatology, Journal Year: 2023, Volume and Issue: 32(8), P. 1204 - 1218

Published: Feb. 13, 2023

Generalized pustular psoriasis (GPP) is a rare subset of involving episodes sterile pustules accompanied by inflammation and, often, systemic involvement. The inflammatory nature GPP has potential for severe multisystem complications including high-output cardiac failure, infections, digestive system issues, and disfiguring or lethal acute flare episodes. disease tends to have higher prevalence in females Asians. IL-1/IL-36 pathway critical facet GPP's pathology. Genetic mutations that are associated with include modifications Interleukin 36 Receptor Antagonist (IL36RN), Caspase Recruitment Domain Family Member 14 (CARD14), Adaptor Related Protein Complex 1 Subunit Sigma 3 (AP1S3), Myeloperoxidase (MPO) Serpin Peptidase Inhibitor Clade A (SERPINA3) genes. Treatment guidelines not well-entrenched. Currently, only one GPP-specific treatment, the interleukin-36 receptor antagonist (IL-36Ra) spesolimab, been approved use United States. Additional anti-IL-36 therapies currently being developed. Other treatment options other biologic such as IL-17 inhibitors, IL-23 inhibitors TNFα inhibitors. Non-biologic therapeutic retinoids, cyclosporine methotrexate. differ throughout world; most countries utilize methotrexate first-line non-biologic options. China Kingdom no use, while several Japan. This review aims serve an update on current global management also relevant aspects pathogenesis, diagnosis, clinical presentation, histopathology, aetiology epidemiology.

Language: Английский

---

Inflammation and Psoriasis: A Comprehensive Review

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16095 - 16095

Published: Nov. 8, 2023

Psoriasis is an immune-mediated disease with a strong genetic component that brings many challenges to sick individuals, such as chronic illness, and which has multiple associated comorbidities like cardiovascular disease, metabolic syndrome, inflammatory bowel psychological disorders. Understanding the interplay between innate adaptative immune system led discovery of specific cytokine circuits (Tumor Necrosis Factor-alpha (TNF-α), IL-23, IL-17), allowed scientists discover new biomarkers can be used predictors treatment response pave way for personalized treatments. In this review, we describe footprint psoriasis leaves on skin beyond, key pathophysiological mechanisms, current available therapeutic options, drawbacks faced by existing therapies, anticipate potential future perspectives may improve quality life affected individuals.

Language: Английский

---

Immunopathogenesis of Atopic Dermatitis: Focus on Interleukins as Disease Drivers and Therapeutic Targets for Novel Treatments

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(1), P. 781 - 781

Published: Jan. 2, 2023

Atopic dermatitis is a chronic, recurrent inflammatory skin disorder manifesting by eczematous lesions and intense pruritus. develops primarily as result of an epidermal barrier defect immunological imbalance. Advances in understanding these pathogenetic hallmarks, particularly the complex role interleukins atopic drivers, resulted achieving significant therapeutic breakthroughs. Novel medications involve monoclonal antibodies specifically blocking function selected small molecules such Janus kinase inhibitors limiting downstream signaling to reduce expression wider array proinflammatory factors. Nevertheless, subset patients remains refractory those treatments, highlighting complexity immunopathogenesis different populations. In this review, we address heterogeneity endotypes phenotypes present novel interleukin-oriented therapies for disease.

Language: Английский

---

Crosstalk: keratinocytes and immune cells in psoriasis

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 9, 2023

In the past, psoriasis was considered a skin disease caused only by keratinocyte disorders. However, efficacy of immunosuppressive drugs and biologics used to treat proves that is an immune-mediated disease. Indeed, variety immune cells are involved in pathogenesis psoriasis, including dendritic cells, Th17 resident memory T cells. Furthermore, keratinocytes play role development as secreting antibacterial peptides, chemokines, tumor necrosis factor-α, interleukin (IL)-36, IL-23. These interact drive aberrant differentiation proliferation keratinocytes. This crosstalk between critical forms inflammatory loop, resulting persistence or exacerbation plaques.

Language: Английский

---

The Role of the Interleukin-1 Family in Complications of Prematurity

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2795 - 2795

Published: Feb. 1, 2023

Preterm birth is a major contributor to neonatal morbidity and mortality. Complications of prematurity such as bronchopulmonary dysplasia (BPD, affecting the lung), pulmonary hypertension associated with BPD (BPD-PH, heart), white matter injury (WMI, brain), retinopathy (ROP, eyes), necrotizing enterocolitis (NEC, gut) sepsis are among causes long-term in infants born prematurely. Though origins multifactorial, inflammation particular imbalance pro- anti-inflammatory mediators now recognized key driver pathophysiology underlying these illnesses. Here, we review involvement interleukin (IL)-1 family perinatal its clinical implications, focus on potential cytokines therapeutic targets for development safe effective treatments early life inflammatory diseases.

Language: Английский

---

The role of interleukin‐36 in health and disease states

Journal of the European Academy of Dermatology and Venereology, Journal Year: 2024, Volume and Issue: 38(10), P. 1910 - 1925

Published: May 23, 2024

Abstract The interleukin (IL)‐1 superfamily upregulates immune responses and maintains homeostasis between the innate adaptive systems. Within IL‐1 superfamily, IL‐36 plays a pivotal role in both responses. Of four isoforms, three have agonist activity (IL‐36α, IL‐36β, IL‐36γ) fourth has antagonist (IL‐36 receptor [IL‐36Ra]). All isoforms bind to (IL‐36R). Binding of IL‐36α/β/γ IL‐36R recruits accessory protein (IL‐1RAcP) activates downstream signalling pathways mediated by nuclear transcription factor kappa B mitogen‐activated kinase pathways. Antagonist binding IL‐36Ra inhibits recruitment IL‐1RAcP, blocking Changes balance within cytokine family can lead uncontrolled inflammatory throughout body. As such, been implicated numerous diseases, notably type pustular psoriasis called generalized (GPP), chronic, rare, potentially life‐threatening, multisystemic skin disease characterised recurrent fever extensive sterile pustules. In GPP, is central pathogenesis, prevention IL‐36‐mediated improve clinical outcomes. this review, we summarize literature describing biological functions pathway. We also consider evidence for activation pathway wide range (e.g., plaque psoriasis, hidradenitis suppurativa, acne, Netherton syndrome, atopic dermatitis pyoderma gangrenosum), lung idiopathic pulmonary fibrosis), gut intestinal fibrosis, bowel Hirschsprung's disease), kidney renal tubulointerstitial lesions) infectious diseases caused variety pathogens COVID‐19; Mycobacterium tuberculosis , Pseudomonas aeruginosa Streptococcus pneumoniae infections), as well cancer. how targeting could be used treating states.

Language: Английский

---

The Role of Long Non-Coding RNA in the Pathogenesis of Psoriasis

Non-Coding RNA, Journal Year: 2025, Volume and Issue: 11(1), P. 7 - 7

Published: Jan. 17, 2025

Psoriasis is a chronic immune-mediated disease with complex pathogenesis. The altered proliferation and differentiation of keratinocytes, together the activity dendritic cells T cells, are crucial drivers psoriasis progression. Long non-coding RNAs (lncRNAs) composed over 200 nucleotides exert large variety functions, including regulation gene expression. Under pathological conditions, expression lncRNAs frequently dysregulated. Recent studies demonstrated that significantly affect major cellular processes, their aberrant likely involved in pathogenesis various disorders. In this review, we will discuss role pathophysiology psoriasis. We summarize recent investigated relationships between keratinocyte pro-inflammatory responses.

Language: Английский

---