IL-36 activity during skin infections

皮肤感染期间 IL-36 的活性

• 批准号: 10809204
• 负责人: LISELOTTE E JENSEN
• 金额: $ 38.36万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-18 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10809204
• 关键词: Acute; Affect; Amino Acids; Atopic Dermatitis; Automobile Driving; Biological Models; Cathepsin G; Cell Culture Techniques; Cells; Chronic; Chronic Disease; Clinical Trials; Data; Decision Making; Development; Disease; Endoplasmic Reticulum; Epidermis; Exposure to; Genes; Herpesvirus 1; Immune; Immunity; Infection; Infectious Skin Diseases; Inflammation; Inflammatory; Interferons; Interleukin-1; Interleukins; Investigation; Knowledge; Link; Messenger RNA; Modeling; Mus; Natural Killer Cells; Patients; Peptide Hydrolases; Peptide Signal Sequences; Pharmaceutical Preparations; Physiological; Protein Isoforms; Proteins; Proteolytic Processing; Psoriasis; Research; Risk; Role; Simplexvirus; Skin; Source; Staphylococcus aureus; Staphylococcus aureus infection; Testing; Time; Tissues; chronic inflammatory disease; cytokine; drug development; extracellular; human disease; improved; in vivo; insight; mouse model; neutralizing antibody; receptor; recruit; response; skin disorder; small molecule; targeted treatment

SUMMARY Interleukin-36 (IL-36) represents IL-36a, IL-36b and IL-36g, which are related to IL-1a and IL-1b. The IL-36 cytokines are increasingly being linked to inflammatory conditions due to elevated expression in affected tissues; however, our understanding of how these cytokines are activated and inactivated remain limited. This knowledge gap hinders informed decision making when starting clinical trials involving IL-36 receptor neutralizing antibodies and the development of cheaper small molecule drugs. We have extensively studied how the IL-36s and IL-1s promote inflammation and immunity during infections and chronic diseases. For example, we showed how they regulate protective immunity through modulation of interferon responses and recruit immune cells to the epidermis in the skin through induction of cytokines and their receptors. These studies involved models of atopic dermatitis, psoriasis, and herpes simplex virus-1 and Staphylococcus aureus infections. Pursuing new directions, we will here examine activation and inactivation mechanisms. Thus, this project will improve our understanding of IL-36 functions. The gained insight will help guide clinical trials aimed at neutralizing IL-36 and set the stage for targeted approaches involving small molecules.

总结 白细胞介素-36（IL-36）代表IL-36 a、IL-36 b和IL-36 g，它们与IL-1a和IL-1b相关。IL-36 细胞因子越来越多地与炎性疾病有关， 然而，我们对这些细胞因子如何被激活和失活的理解仍然有限。这 知识差距阻碍了在开始涉及IL-36受体的临床试验时做出明智的决策 中和抗体和开发更便宜的小分子药物。我们广泛研究了 IL-36和IL-1如何在感染和慢性疾病期间促进炎症和免疫。为 例如，我们展示了它们如何通过调节干扰素反应来调节保护性免疫， 通过诱导细胞因子及其受体将免疫细胞募集到皮肤的表皮。这些 研究涉及特应性皮炎、银屑病、单纯疱疹病毒-1和金黄色葡萄球菌模型 感染.为了追求新的方向，我们将在这里研究激活和失活机制。因此， 该项目将提高我们对IL-36功能的理解。所获得的见解将有助于指导临床试验， 中和IL-36，并为涉及小分子的靶向方法奠定基础。