Last update 01 Nov 2024

IL-23p19 x IL-6

Last update 01 Nov 2024

Basic Info

Related Targets

IL-23p19IL-6

Drugs associated with IL-23p19 x IL-6

AZ-17

Target

IL-23p19 x IL-6

Mechanism

IL-23p19 inhibitors [+1]

Active Org.-

Originator Org.

Allozyne, Inc.

Active Indication-

Inactive Indication

Psoriasis

Drug Highest PhaseDiscontinued

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with IL-23p19 x IL-6

100 Translational Medicine associated with IL-23p19 x IL-6

0 Patents (Medical) associated with IL-23p19 x IL-6

234

Literatures (Medical) associated with IL-23p19 x IL-6

01 Aug 2024·Acta Biomaterialia

Innate lymphoid cell-based immunomodulatory hydrogel microspheres containing Cutibacterium acnes extracellular vesicles for the treatment of psoriasis

Article

Author: Zhang, Chunhua ; Zhou, Zhiyang ; Cheng, Biao ; Gan, Yuyang ; Wang, Gaofeng ; Qi, Fangfang ; Lu, Xinyu ; Wang, Hailin ; Zhang, Xiaofei ; Hu, Zhiqi ; Xu, Yujie ; Wang, Xusheng ; Lu, Feng ; Zeng, Dongqiang ; Li, Yue ; Zhang, Jiarui

Psoriasis is a chronic skin inflammation influenced by dysregulated skin microbiota, with the role of microbiota in psoriasis gaining increasing prominence. Bacterial extracellular vesicles (bEVs) serve as crucial regulators in the interaction between hosts and microbiota. However, the mechanism underlying the therapeutic potential of bEVs from commensal bacteria in psoriasis remains unclear. Here, we investigated the therapeutic role of Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs) in psoriasis treatment. To prolong the active duration of CA-EVs, we encapsulated them in gelatin methacrylate (GelMA) to fabricate hydrogel microspheres (CA-EVs@GHM) with sustained release properties. As GelMA degraded, CA-EVs were gradually released, maintaining a high concentration in mouse skin even 96 h post-treatment. In human keratinocyte cells (HaCaT), CA-EVs@GHM enhanced resistance to Staphylococcus aureus (S. aureus), promoted proliferation and migration of HaCaT cells exposed to S. aureus, and significantly reduced the expression of inflammatory genes such as interleukin (IL)-6 and C-X-C motif chemokine ligand 8 (CXCL8). In vivo, CA-EVs@GHM, more potent than CA-EVs alone, markedly attenuated proinflammatory gene expression, including tumor necrosis factor (TNF), Il6, Il17a, Il22 and Il23a in imiquimod (IMQ)-induced psoriasis-like mice, and restored skin barrier function. 16S rRNA sequencing revealed that CA-EVs@GHM might provide therapeutic effects against psoriasis by restoring microbiota diversity on the back skin of mice, reducing Staphylococcus colonization, and augmenting lipid metabolism. Furthermore, flow cytometry analysis showed that CA-EVs@GHM prevented the conversion of type 2 innate lymphoid cells (ILC2) to type 3 innate lymphoid cells (ILC3) in psoriasis-like mouse skin, reducing the pathogenic ILC3 population and suppressing the secretion of IL-17 and IL-22. In summary, our findings demonstrate that the long-term sustained release of CA-EVs alleviated psoriasis symptoms by controlling the transformation of innate lymphoid cells (ILCs) subgroups and restoring skin microbiota homeostasis, thus offering a promising therapy for psoriasis treatment. STATEMENT OF SIGNIFICANCE: Cutibacterium acnes, which is reduced in psoriasis skin, has been reported to promote skin homeostasis by regulating immune balance. Compared to live bacteria, bacterial extracellular vesicles (bEVs) are less prone to toxicity and safety concerns. bEVs play a pivotal role in maintaining bacterial homeostasis and modulating the immune system. However,bEVs without sustained release materials are unable to function continuously in chronic diseases. Therefore, we utilized hydrogel microspheres to encapsulate Cutibacterium acnes (C. acnes)-derived extracellular vesicles (CA-EVs), enabling long term sustained release. Our findings indicate that, CA-EVs loaded gelatin methacrylate hydrogel microspheres (CA-EVs@GHM) showed superior therapeutic effects in treating psoriasis compared to CA-EVs. CA-EVs@GHM exhibited a more significant regulation of pathological type 3 innate lymphoid cells (ILC3) and skin microbiota, providing a promising approach for microbiota-derived extracellular vesicle therapy in the treatment of skin inflammation.

01 Aug 2024·Journal of Interferon & Cytokine Research

Cytokine Signatures and Immune Dysregulation in COVID-19 Patients: Transcriptomic and Serum Analysis

Article

Author: Fagone, Paolo ; Petralia, Maria Cristina ; Mihaylova, Nikolina ; Doneva, Yana Valerieva ; Bradyanova, Silviya Lyubenova ; Nicoletti, Ferdinando ; Muñoz-Valle, José Francisco ; Tchorbanov, Andrey Ivanov ; Ralchev, Nikola ; Elefterova-Florova, Elena Vikentieva

COVID-19, caused by the SARS-CoV-2 virus, has caused a global health crisis, necessitating a deeper understanding of its pathophysiology. In this study, we explored the immune and hematological dynamics in COVID-19 patients to gain insights into disease severity and prognosis. Our findings revealed distinct cytokine profiles in moderate and severe cases. IL12A was significantly upregulated in peripheral blood mononuclear cells from moderate cases, suggesting a potential role in initiating an effective immune response. Conversely, severe cases exhibited downregulation of key pro-inflammatory cytokines (IL23A, TNFalpha, IL1B, and IFNG) alongside an upregulation of the immunosuppressive IL10, indicative of a dysregulated immune environment. Serum analysis showed elevated IL6 and IL10 levels in both moderate and severe cases, emphasizing their potential as markers for disease severity. Notably, no significant differences in serum cytokines were found between recovery and lethal cases. In lethal cases of COVID-19, elevated D-dimer, urea, and creatinine correlated with IL6 and IL10. This study contributes valuable information to the ongoing efforts to understand and manage the dysregulated immune responses underlying COVID-19 pathology.

30 Jun 2024·Cureus

Weighted Gene Co-expression Network Analysis of the Inflammatory Wnt Signaling Reveals Biomarkers Related to Bone Formation

Article

Author: Suresh, Ramya ; Ramadoss, Ramya ; Yadalam, Pradeep Kumar

Background and aim Osteocytes regulate bone metabolism and balance through various mechanisms, including the Wnt (Wingless-related integration site signal transduction) signaling pathway. Weighted gene co-expression network analysis (WGCNA) is a computational method to identify functionally related genes based on expression patterns, especially in the Wnt-beta-catenin and osteo-regenerative pathways. This study aims to analyze gene modules of the Wnt signaling pathway from WGCNA analysis. Methods The study used a microarray dataset from the GEO (GSE228306) to analyze differential gene expression in human primary monocytes. The study standardized datasets using Robust Multi-Array Average (RMA) expression measure and Integrated Differential Expression and Pathway (IDEP) analysis tool, building a co-expression network for group-specific component (GC) genes. Results The study uses WGCNA to identify co-expression modules with dysregulated mRNAs, revealing enrichment in Wnt-associated pathways and top hub-enriched genes like colony-stimulating factor 3 (CSF3), interleukin-6 (IL-6), IL-23 subunit alpha (IL23A), suppressor of cytokine signaling 1 (SOCS1), and C-C motif chemokine ligand 19 (CCL19). Conclusion WGCNA analysis of the Wnt signaling pathway will involve functional annotation, network visualization, validation, integration with other omics data, and addressing method limitations for better understanding.

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