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.

概括 白介素-36（IL-36）代表与IL-1A和IL-1B有关的IL-36A，IL-36B和IL-36G。 IL-36 由于受影响 组织；但是，我们对这些细胞因子如何被激活和灭活的理解仍然有限。这 知识差距阻碍在启动涉及IL-36受体的临床试验时，有明智的决策做出 中和抗体和较便宜的小分子药物的发展。我们已经进行了广泛的研究 IL-36和IL-1如何促进感染和慢性疾病期间的炎症和免疫力。为了 例如，我们展示了它们如何通过调节干扰素反应和 通过诱导细胞因子及其受体，将免疫细胞募集到皮肤表皮中。这些 研究涉及特征性皮炎，牛皮癣和单纯疱疹病毒和金黄色葡萄球菌的模型 感染。追求新的方向，我们将在这里检查激活和灭活机制。因此，这个 项目将提高我们对IL-36功能的理解。获得的见解将有助于指导针对的临床试验 在中和IL-36处，并为涉及小分子的靶向方法奠定了基础。