Lipocalin-2 expression identifies an intestinal regulatory neutrophil population during acute graft-versus-host disease

Science Translational Medicine, Journal Year: 2024, Volume and Issue: 16(735)

Published: Feb. 21, 2024

Acute graft-versus-host disease (aGVHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT), for which therapeutic options are limited. Strategies to promote intestinal tissue tolerance during aGVHD may improve patient outcomes. Using single-cell RNA sequencing, we identified lipocalin-2 (LCN2)–expressing neutrophil population in mice with aGVHD. Transfer LCN2-overexpressing neutrophils or treatment recombinant LCN2 reduced severity, whereas the lack epithelial enhanced severity and caused microbiome alterations. Mechanistically, induced insulin-like growth factor 1 receptor (IGF-1R) signaling macrophages through SLC22A17, increased interleukin-10 (IL-10) production major histocompatibility complex class II (MHCII) expression. LCN2-pretreated but did not reduce graft-versus-leukemia effects. Furthermore, expression correlated IL-10 biopsies multiple cohorts patients aGVHD, IGF-1R human macrophages. Collectively, LCN2-expressing that by decreasing MHCII increasing This work provides foundation administration as approach

Language: Английский

---

Immune cells in the epithelial immune microenvironment of psoriasis: emerging therapeutic targets

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 4, 2024

Psoriasis is a chronic autoimmune inflammatory disease characterized by erroneous metabolism of keratinocytes. The development psoriasis closely related to abnormal activation and disorders the immune system. Dysregulated skin protective mechanisms can activate pathways within epithelial microenvironment (EIME), leading autoimmune-related diseases. In this review, we initially emphasized pathogenesis psoriasis, paying particular attention interactions between cells production cytokines in psoriasis. Subsequently, delved into significance EIME emergence A thorough understanding these processes crucial targeted therapies for Finally, discussed potential novel aimed at modulating This comprehensive examination sheds light on intricate underlying provides insights therapeutic avenues immune-mediated

Language: Английский

---

Alleviative effects of combined topical melatonin and rutin on imiquimod-induced psoriasis mouse model

Pharmacia, Journal Year: 2024, Volume and Issue: 71, P. 1 - 13

Published: Sept. 3, 2024

Background : Psoriasis is a longstanding autoimmune dermatosis with thickened, reddish-brown, and flaking skin lesions. Melatonin an indolamine hormone exhibiting antioxidant, anti-inflammatory, anti-proliferative actions. Rutin nutritional flavonoid possessing antioxidative, immunomodulatory properties. Aim To explore the potential anti-psoriatic activity of combined topical melatonin rutin. Methods 70 albino mice were divided into 7 groups 10 each. The impacts clinical observation, histopathological examination, biomarker analysis estimated. Results Combined rutin effectively diminished imiquimod-induced elevated PASI Baker’s scores corrected aberrations. Diminished inflammatory indicators like TNF-α IL-17A, angiogenic elements VEGF, oxidative MDA, proliferative Ki-67 also noted. Conclusion have profound effects.

Language: Английский

---

Inhibition of the JAK-STAT Pathway in the Treatment of Psoriasis: A Review of the Literature

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4681 - 4681

Published: April 25, 2024

Psoriasis is a highly prevalent dermatological disease associated with an increased systemic inflammatory response. In addition, joint involvement also present in around 20% of patients. Therefore, treatment modalities used this condition should be simultaneously effective at improving skin manifestations, reducing inflammation, and addressing psoriatic arthritis when present. Twenty years ago, the introduction biologic treatments for psoriasis was turning point management condition, offering reasonably safe option patients whose could not adequately controlled conventional therapies. At moment, Janus Kinase inhibitors (JAKis) are new class promising molecules psoriasis. They orally administered can show benefits who failed therapy. We conducted scoping review order to identify randomized-controlled trials that investigated different JAKis plaque arthritis, emphasis on have been approved by European Medicines Agency Food Drug Administration. The added value study it collected information about two indications, provide integrated understanding range effects whole spectrum manifestations.

Language: Английский

---

Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis

Journal of Personalized Medicine, Journal Year: 2024, Volume and Issue: 14(5), P. 535 - 535

Published: May 16, 2024

Psoriasis is a chronic recurrent inflammatory autoimmune pathology with significant genetic component and several interferences of immunological cells their cytokines. The complex orchestration psoriasis pathogenesis related to the synergic effect immune cells, polygenic alterations, autoantigens, other external factors. major act IL-23/IL-17 axis, strongly influencing pattern established during disease activity, visible as continuous perpetuation pro-inflammatory response keratinocyte activation proliferation, leading development psoriatic lesions. Genome-wide association studies (GWASs) offer better view pathogenic pathways, approximately one-third psoriasis’s impact on associated MHC region, loci located chromosome 6. most eloquent factor psoriasis, PSORS1, was identified in I site. Among factors involved its etiology, dysbiosis, due or stimulus, induces burst consequences; both cutaneous gut microbiome get process. Cutting-edge research comprehensive insights into pathogenesis, fostering novel genetic, epigenetic, factors, have generated spectacular improvement over past decades, securing path toward specific targeted immunotherapeutic approach delayed progression arthritis. This review aimed insight various domains that underline how they influence evolution. mechanism multifaceted involves an interplay cellular humoral immunity, which affects susceptible microbiota background. An in-depth understanding role forms basis for developing individualized therapeutic targets can improve management.

Language: Английский

---

Comparative activity of dimethyl fumarate derivative IDMF in three models relevant to multiple sclerosis and psoriasis

FEBS Open Bio, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Dimethyl fumarate (DMF) is an anti‐inflammatory and immunoregulatory medication used to treat multiple sclerosis (MS) psoriasis. Its skin sensitization property precludes its topical use, which unfortunate for the treatment of Isosorbide di‐(methyl fumarate) (IDMF), a novel derivative DMF, was synthesized circumvent this adverse reaction unlock potential delivery, could be useful treating psoriasis in subpopulation psoriatic MS patients, as well general population. Here, we compared therapeutic non‐sensitizing with DMF version Diroximel three skin‐ neuroinflammation models: lck‐GFP zebrafish, activated BV‐2 murine microglia human T‐lymphocyte Jurkat cell line. The results provide comparative evaluation bioactivity these related chemical entities models relevant expose several advantages unique IDMF.

Language: Английский

---

RNAi-based ALOX15B silencing augments keratinocyte inflammation in vitro via EGFR/STAT1/JAK1 signalling

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 22, 2025

Abstract Arachidonate 15-lipoxygenase type B (ALOX15B) peroxidises polyunsaturated fatty acids to their corresponding acid hydroperoxides, which are subsequently reduced into hydroxy-fatty acids. A dysregulated abundance of these biological lipid mediators has been reported in the skin and blood psoriatic compared healthy individuals. RNAscope immunohistochemistry revealed increased ALOX15B expression lesional psoriasis samples. Using a cytokine cocktail containing IL-17A, interferon-gamma tumour necrosis factor-alpha produce psoriasis-like phenotype, role for human epidermal keratinocyte inflammation was investigated. siRNA-mediated silencing CCL2 secretion. In addition CCL2, secretion CCL5 CXCL10 were elevated equivalents treated with lipoxygenase inhibitor ML351. Inhibition JAK1/STAT1 pathway reversed enhanced found silencing. Previous studies have linked growth factor receptor (EGFR) inhibition upregulation cytokines including CXCL10. EGFR signalling potentiated effect on expression. Confirming previous findings, gene cholesterol biosynthesis genes via ERK phosphorylation. Reduced phosphorylation dependant NRF2 activation. Furthermore, plasma membrane lipids investigated confocal microscopy, revealing rafts. This study suggests through modulation peroxidation EGFR/JAK1/STAT1 axis.

Language: Английский

---

Adalimumab induced psoriasis in Crohn’s disease and treatment with ustekinumab: case report and special histopathological findings

Frontiers in Medicine, Journal Year: 2025, Volume and Issue: 11

Published: Jan. 24, 2025

This case report presents an instance of Tumor Necrosis Factor- α Inhibitor-induced psoriasis (TNFiIP), also known as paradoxical psoriasis, in a 30-year-old male with fistulizing Crohn’s disease. The patient developed extensive erythematous and scaly lesions on the palms, lower limbs, ankles, soles after 4 months adalimumab monotherapy. Histopathological analysis revealed pattern psoriasiform dermatitis notable dermal neutrophil eosinophil infiltration, distinguishing TNFiIP from idiopathic psoriasis. patient’s condition significantly improved following transition to ustekinumab, which highlights importance alternative therapeutic strategies for patients who exhibit reactions TNF- inhibitors.

Language: Английский

---

Causal Relationship Between Psoriasis and Bullous Pemphigoid: A Mendelian Randomization Analysis

Dermatology Practical & Conceptual, Journal Year: 2025, Volume and Issue: 15(1), P. 4458 - 4458

Published: Jan. 29, 2025

Introduction: Psoriasis and bullous pemphigoid (BP) are the 2 major types of immune-mediated inflammatory skin diseases. Studies have reported association between psoriasis BP; however, no studies whether a causal relationship exists these Objectives: In order to explore BP, we performed bidirectional two-sample Mendelian randomization (MR) study. Methods: Genome-wide study (GWAS) data related BP were collected. The inverse variance weighted (IVW) method was primarily applied for our MR analysis, MR-Egger, median, simple mode, mode methods used additionally. Heterogeneity, horizontal pleiotropy, potential outliers assessed analysis results. Results: GWAS (3 cohorts) (1 cohort) from publicly available trials selected. Our results showed that causally associated with could increase risk reversed has effect on psoriasis. No heterogeneity or pleiotropy detected. Conclusion: These findings provided new evidence suggested is potentially which help us improving treatment strategy patients mechanism remains open further investigation.

Language: Английский

---

Wnt signaling as a translational target in rheumatoid and psoriatic arthritis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Feb. 4, 2025

Rheumatoid arthritis (RA) and Psoriatic (PsA) are chronic inflammatory diseases mainly affecting joints. RA primarily targets the synovial joints is characterized by cartilage bone erosion, whereas PsA associated with skin nail psoriasis erosive damage an exuberant formation soft tissue involvement. Recent evidence described involvement of Wnt pathway in pathogenesis these diseases. Thus, we aimed to analyze some components signaling, i.e. DKK1, 5a β-catenin, their association disease activity indices, investigating possible differences between two Sera from 18 patients naïve for biological therapy, 20 matched healthy donors (HD) were tested DKK1 ELISA, β-catenin Immunoblotting. Values correlated CTX-1, detected indices: Disease Activity Score on 28 (DAS28-CRP) Arthritis (DAPSA) score PsA. This study highlights significant increase 5a, levels compared HD, distinct patterns correlation indices. Indeed, patients, positively DAS28-CRP score, negatively DAPSA score. Our findings showed a strong CTX-1 supporting relationship presence joint erosions. Furthermore, positive was found IL-6 RA, indicating that may be involved cascade. compares signaling PsA, suggesting represent mechanism activity. In particular, it indicates marker resorption, patients. These underscore importance biomarkers potential monitoring offering insights into mechanisms therapeutic targets.

Language: Английский

---