Innate immune regulation of neuroinflammation

神经炎症的先天免疫调节

• 批准号: 10621194
• 负责人: Gregory F Sonnenberg
• 金额: $ 61.05万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10621194
• 关键词: Address; Affect; Age-associated memory impairment; Alzheimer' s Disease; American; Amyotrophic Lateral Sclerosis; Antigen Presentation; Antigen Targeting; Autoimmune; B-Lymphocytes; CD4 Positive T Lymphocytes; Cell Maturation; Cells; Central Nervous System; Circulation; Clinical; Clinical Research; Coculture Techniques; Critical Pathways; Cytokine Receptors; Data; Demyelinating Diseases; Dendritic Cells; Disease; Exhibits; Experimental Models; Family; Gene Expression Profile; Health Care Costs; Histocompatibility Antigens Class II; Homing; IL17 gene; Immunity; In Vitro; Infiltration; Inflammation; Inflammatory; Innate Immune System; Intestines; Knowledge; Lymphocyte; Lymphoid Cell; Mediating; Multiple Sclerosis; Mus; Myelin; Neurodegenerative Disorders; Parkinson Disease; Pathogenesis; Pathway interactions; Patients; Peripheral; Population; Production; Regulation; Research Proposals; Role; Sampling; Specific qualifier value; T cell infiltration; T cell response; T-Lymphocyte; Testing; Therapeutic; Tissues; Translating; adaptive immunity; cell growth regulation; cell type; curative treatments; cytokine; gut inflammation; immunoregulation; in vivo; innovation; mouse model; mucosal site; multiple sclerosis patient; neuroinflammation; next generation; novel; novel strategies; prevent; progenitor; receptor; response; tool; transcription factor; translational study; treatment strategy

PROJECT ABSTRACT Inflammation in the central nervous system (CNS) is causally associated with the pathogenesis and progression of multiple demyelinating and neurodegenerative diseases, including Multiple Sclerosis (MS), Parkinson's Disease, Alzheimer's Disease, Amyotrophic Lateral Sclerosis, and general age-associated cognitive decline Therefore, there is an urgent need to develop novel approaches to prevent, limit or reverse neuroinflammation. Basic, translation and clinical studies indicate that T cells can be major drivers of inflammation in the CNS, but the mechanisms promoting or inhibiting these responses remain poorly defined. The fundamental focus of this research proposal is to: (i) interrogate a novel pathway by which the innate immune system controls T cell responses in the CNS, (ii) understand the regulation of these cellular interactions, and (iii) define whether it is possible to harness this or related pathways for therapeutic benefit in neuroinflammation. We will employ innovative approaches and develop new tools to address these fundamental gaps in knowledge, and where possible, translate our findings from mice into clinically defined patient samples. Results from these studies will advance our understanding of the pathways that promote or inhibit pro-inflammatory T cell responses in the CNS, and could provoke the next generation of novel preventative, therapeutic or curative treatment strategies for demyelinating and neurodegenerative diseases.

项目摘要 中枢神经系统（CNS）中的炎症与发病机制有因果关系， 多种脱髓鞘和神经退行性疾病的进展，包括多发性硬化症（MS）， 帕金森氏病、阿尔茨海默氏病、肌萎缩侧索硬化症和一般年龄相关性 因此，迫切需要开发新的方法来预防、限制或逆转 神经炎症基础、转化和临床研究表明，T细胞可能是免疫应答的主要驱动力。 这些反应是中枢神经系统炎症反应的一个重要组成部分，但促进或抑制这些反应的机制仍不清楚。 这项研究的基本重点是：（一）询问一种新的途径，通过这种途径， 先天免疫系统控制T细胞反应在中枢神经系统，（ii）了解这些调控 细胞相互作用，以及（iii）确定是否有可能利用这种或相关的途径， 在神经炎症中的治疗益处。我们将采用创新方法，开发新工具， 解决这些基本的知识差距，并在可能的情况下，将我们在小鼠身上的发现转化为 临床定义的患者样本。这些研究的结果将促进我们对 促进或抑制CNS中促炎性T细胞反应的途径，并可能引发 下一代新的预防性、治疗性或治愈性脱髓鞘治疗策略 和神经退行性疾病。

项目成果

Epsilon toxin-producing Clostridium perfringens colonize the multiple sclerosis gut microbiome overcoming CNS immune privilege.

• DOI: 10.1172/jci163239
• 发表时间: 2023-05-01
• 期刊: JOURNAL OF CLINICAL INVESTIGATION
• 影响因子: 15.9
• 作者: Ma, Yinghua;Sannino, David;Linden, Jennifer R.;Haigh, Sylvia;Zhao, Baohua;Grigg, John B.;Zumbo, Paul;Duendar, Friederike;Butler, Daniel;Profaci, Caterina P.;Telesford, Kiel;Winokur, Paige N.;Rumah, Kareem R.;Gauthier, Susan A.;Fischetti, Vincent A.;McClane, Bruce A.;Uzal, Francisco A.;Zexter, Lily;Mazzucco, Michael;Rudick, Richard;Danko, David;Balmuth, Evan;Nealon, Nancy;Perumal, Jai;Kaunzner, Ulrike;Brito, Ilana L.;Chen, Zhengming;Xiang, Jenny Z.;Betel, Doron;Daneman, Richard;Sonnenberg, Gregory F.;Mason, Christopher E.;Vartanian, Timothy
• 通讯作者: Vartanian, Timothy