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Dynamic Control of Innate Antiviral Immunity in Skin Homeostasis and Inflammation

皮肤稳态和炎症中先天抗病毒免疫的动态控制

基本信息

批准号：
10686699
负责人：
Jennifer Yunyan Zhang
金额：
$ 45.08万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-11 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10686699
关键词：
Ablation Acyclovir Address Antimicrobial Resistance Antiviral Agents Antiviral Response Antiviral resistance Atopic Dermatitis Binding Biological Assay Bite C Fiber Caliber Cells Clinical Competence Cues Culicidae Cutaneous Dendritic Cells Elderly Epidermis Epithelial Epithelial Cells Family member Genes Genetic Transcription Goals Heterogeneity Homeostasis Host Defense Human IRF3 gene Immune system Immunity Immunologics In Vitro Inflammation Integration Host Factors Interferon Type I Interferons Interleukin-12 Knockout Mice Knowledge Ligation Light Mediating Modeling Molecular Mus Natural Immunity Nerve Fibers Neurons Neurotransmitters Neutropenia Operative Surgical Procedures Outcome Paraplegia Pathway interactions Patients Pharmacology Play Predisposition Prevention Production Proteins Recombinant Interferon Regulation Resistance Role STAT1 gene Sensory Signal Pathway Signal Transduction Skin Skin injury Spinal Ganglia System TNF receptor-associated factor 3 Testing Therapeutic Toxic effect Trauma Viral Virus Virus Diseases Work adaptive immune response antimicrobial antiviral immunity defined contribution gene induction high risk in vivo infection rate innovation keratinocyte knock-down loss of function mutation neonate nephrotoxicity neurosensory new therapeutic target novel novel therapeutics pathogenic virus patient population prevent protein expression receptor relating to nervous system single cell sequencing targeted treatment transcription factor

项目摘要

Project Summary Loss-of-function mutations and suppression of innate antiviral proteins, such as OAS2 and OASL are associated with high viral infection rates in mice and humans. Because of their induction by interferons, these antiviral proteins are often referred to as interferon-stimulated genes (ISG). While recombinant interferon stimulates production of these antiviral proteins, type I interferon’s severe toxicity is the major limitation in its therapeutic utility. Additionally, pharmacological antivirals, such as acyclovir, have a high risk for triggering neutropenia and nephrotoxicity in vulnerable patient populations. Therefore, there is a significant unmet clinical need for new antiviral therapeutics. This need can be addressed by developing a full understanding of interferon-independent regulation of endogenous antiviral proteins and identifying targets for therapy and prevention by activation of this incredibly potent natural antiviral pathway. Our proposed work will answer important question: 1) Which interferon-independent signals and pathways can induce antiviral competence? 2) Does epithelial antiviral innate immunity differ on a single cell level? 3) What factors collaborate in the induction of innate antiviral immunity?

项目概要功能丧失突变和先天抗病毒蛋白（例如 OAS2 和 OASL）的抑制与高小鼠和人类的病毒感染率。由于干扰素的诱导作用，这些抗病毒蛋白通常被称为干扰素刺激基因（ISG）。虽然重组干扰素刺激这些抗病毒药物的产生 I 型干扰素的严重毒性是其治疗用途的主要限制。此外，药理阿昔洛韦等抗病毒药物极有可能引发易感患者中性粒细胞减少症和肾毒性人口。因此，对新的抗病毒疗法的临床需求存在显着的未满足的需求。这个需求可以是通过全面了解内源性抗病毒蛋白的干扰素非依赖性调节来解决这一问题通过激活这种极其有效的天然抗病毒途径来确定治疗和预防的目标。我们的拟议的工作将回答重要问题：1）哪些独立于干扰素的信号和途径可以诱导抗病毒能力？ 2）上皮抗病毒先天免疫在单细胞水平上是否存在差异？ 3）哪些因素合作诱导先天抗病毒免疫？

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

IL-27 Derived From Macrophages Facilitates IL-15 Production and T Cell Maintenance Following Allergic Hypersensitivity Responses.

DOI：
10.3389/fimmu.2021.713304
发表时间：
2021
期刊：
Frontiers in immunology
影响因子：
7.3
作者：
Suwanpradid J;Lee MJ;Hoang P;Kwock J;Floyd LP;Smith JS;Yin Z;Atwater AR;Rajagopal S;Kedl RM;Corcoran DL;Zhang JY;MacLeod AS
通讯作者：
MacLeod AS

Skin Viral Infections: Host Antiviral Innate Immunity and Viral Immune Evasion.