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

Science Translational Medicine, Год журнала: 2024, Номер 16(735)

Опубликована: Фев. 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

Язык: Английский

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

Frontiers in Immunology, Год журнала: 2024, Номер 14

Опубликована: Янв. 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

Язык: Английский

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

Pharmacia, Год журнала: 2024, Номер 71, С. 1 - 13

Опубликована: Сен. 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.

Язык: Английский

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

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(9), С. 4681 - 4681

Опубликована: Апрель 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.

Язык: Английский

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Review: A Contemporary, Multifaced Insight into Psoriasis Pathogenesis

Journal of Personalized Medicine, Год журнала: 2024, Номер 14(5), С. 535 - 535

Опубликована: Май 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.

Язык: Английский

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

FEBS Open Bio, Год журнала: 2025, Номер unknown

Опубликована: Янв. 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.

Язык: Английский

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

Frontiers in Medicine, Год журнала: 2025, Номер 11

Опубликована: Янв. 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.

Язык: Английский

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miR-16-5p, miR-21-5p, and miR-155-5p in circulating vesicles as psoriasis biomarkers

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 26, 2025

Abstract Psoriasis is a chronic skin disorder marked by fast cell growth, leading to thick, red, scaly patches. MicroRNAs are small, non-coding RNA molecules that play crucial role in post-transcriptional gene regulation. This study investigates miR-16-5p, miR-21-5p, and miR-155-5p expression psoriasis EVs assesses their biomarker potential, exploring associated target genes pathways via bioinformatics. A cross-sectional case-control included 40 patients, with blood samples collected EDTA tubes. from extracellular vesicles was isolated using Qiagen kits, miRNAs were quantified RT-qPCR. Bioinformatic analysis predicted databases like miRDB TargetScan. Gene data GEO processed, differentially expressed identified. assessed patients’ circulating versus controls, finding significantly lower levels patients. ROC confirmed diagnostic potential. positive correlation of miR-16-5p the Area Severity Index (PASI) suggests severity marker Bioinformatics identified 378 common dysregulated genes, revealing key interactions psoriasis. heat map miRNA-mediated suppression disease. identifies as potential biomarkers, addition significant involved pathophysiology.

Язык: Английский

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Topical TYK2 inhibitor ameliorates psoriasis‐like dermatitis via the AKT‐SP1‐NGFR‐AP1 pathway in keratinocytes

Clinical and Translational Medicine, Год журнала: 2025, Номер 15(3)

Опубликована: Март 1, 2025

Tyrosine kinase 2 (TYK2)-dependent cytokine signalling is integral to the pathogenesis of psoriasis. While BMS-986165, a highly selective TYK2 inhibitor, has recently been approved for oral treatment psoriasis, its therapeutic potential via topical application remains unexplored. We aim investigate efficacy topically applying inhibitor in psoriasis and elucidate underlying mechanisms driving effects this delivery approach. 1.5% BMS-986165 ointment was applied back skin imiquimod (IMQ)-induced psoriatic mice. To identify target cells influenced by we performed single cell RNA sequencing (scRNA-seq) flow cytometry on mouse lesions. The role vitro assessed silencing expression or administering human keratinocytes (KCs). Mechanistic insights into function KCs were further investigated using RNA-seq, dual luciferase reporter assay ChIP-qPCR. External use significantly ameliorated IMQ-induced psoriasis-like dermatitis. Importantly, attenuated proinflammatory capability KCs. In vitro, inhibition suppressed transcription nerve growth factor receptor (NGFR) disrupting AKT-SP1 pathway. This impairment hindered activation activator protein 1 (AP1), thereby weakening study reveals novel manner therapy, which might prompt development Crucially, our findings provide an underexplored regulatory mechanism Topical alleviates reduces progression through restraining inflammatory responses keratinocytes. regulates response AKT-SP1-NGFR-AP1

Язык: Английский

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A comparative study between nanostructured lipid carriers and invasomes for the topical delivery of luteolin: Design, optimization and pre-clinical investigations for psoriasis treatment

Journal of Drug Delivery Science and Technology, Год журнала: 2024, Номер 97, С. 105740 - 105740

Опубликована: Май 7, 2024

Язык: Английский

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