Immune mechanisms of pain of the IL-23IL-17 Axis in Inflammatory Arthritis

炎症性关节炎中 IL-23IL-17 轴疼痛的免疫机制

基本信息

批准号：
10861492
负责人：
Iannis Elias Adamopoulos
金额：
$ 24.59万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2025-11-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10861492
关键词：
Afferent Neurons Animal Model Arthritis Autoimmune Diseases Autoimmunity Award Biological Assay C Fiber CCL17 gene Cells Chemicals Chronic Data Data Correlations Data Set Dermal Development Disease Effectiveness Gene Transfer Genetic Complementation Test Granulocyte-Macrophage Colony-Stimulating Factor Hyperalgesia IL17 gene ITGAM gene Imiquimod Immobilization Immune Immunity Inflammation Inflammation Process Inflammatory Inflammatory Arthritis Interleukins Ion Channel Joints Knockout Mice Leukocytes Link Lymphoid Cell Macrophage Mechanics Mediating Mediator Modeling Molecular Molecular Target Monoclonal Antibodies Mus Muscle Musculoskeletal Diseases Myeloid Cells Myelopoiesis Neurogenic Inflammation Neurogenic arthropathy Neurons Neuropathy Neuropeptides Nociception Nociceptors Organ Pain Pain Research Pathogenicity Pathologic Pathway interactions Patients Peripheral Population Process Psoriasis Psoriatic Arthritis Quality of life Reporter Reporting Research Rheumatism Role Signal Transduction Skin Sodium Channel Stimulus Stress T-Lymphocyte TNF gene TRPV channel TRPV1 gene Testing Therapeutic Therapeutic Intervention Tissues Transducers United States National Institutes of Health Vasodilation Vertebral column Work Zymosan allodynia arthropathies autoinflammatory diseases bone cell injury experience experimental study extreme temperature functional disability improved in vivo interest interleukin-23 member neurotransmission novel pleiotropism pressure recruit skin disorder transcriptome transcriptome sequencing transcriptomics γδ T cells

项目摘要

Project Summary/Abstract The IL-23/IL-17 axis is implicated in many autoimmune and autoinflammatory disorders including psoriatic arthritis, a chronic and progressive inflammatory arthritis closely linked with psoriasis. We have been studying the IL-23/IL-17 axis in inflammatory arthritis through the NIH award R01AR062173 and investigated the tissue destructive process of inflammation as it relates to bone and skin degeneration. Herein we propose to study the immune mechanisms of the IL-23/IL- 17 axis in pain as part of the Notice of Special Interest (NOSI): NOT-AR-23-015 Urgent Competitive Revisions to Add Research on Cutting Edge Pain Research in Rheumatic, Skin, and Musculoskeletal Disease. Specifically, this supplement will address the cellular and molecular mechanisms that are responsible for pain. We will therefore adapt the animal models and in conjunction with pain readouts facilitated by our collaborators we will identify the effectors and transducers that mediate immune pain in inflammatory arthritis. Our two specific aims will address the effect of myelopoiesis via GM-CSF+ innate lymphoid cells and the development of IL-17A+ myeloid cells that were recently associated with pain. Our work will uncover the pathogenic mechanisms of immune pain and uncover novel molecular targets that can be exploited for therapeutic intervention and directly benefit arthritis patients worldwide.

项目概要/摘要 IL-23/IL-17 轴与许多自身免疫和自身炎症性疾病有关，包括银屑病关节炎是一种与银屑病密切相关的慢性进行性炎症性关节炎。我们一直在通过 NIH 奖研究炎症性关节炎中的 IL-23/IL-17 轴 R01AR062173 并研究了炎症的组织破坏过程，因为它与骨骼和皮肤退化。在此，我们建议研究IL-23/IL-的免疫机制。 17 轴疼痛作为特别关注通知 (NOSI) 的一部分：NOT-AR-23-015 紧急竞争性修订增加了风湿病、皮肤病和疼痛领域的前沿疼痛研究肌肉骨骼疾病。具体来说，该补充剂将解决细胞和分子问题造成疼痛的机制。因此，我们将调整动物模型并在结合我们的合作者提供的疼痛读数，我们将识别效应器并介导炎症性关节炎免疫疼痛的传感器。我们的两个具体目标将解决 GM-CSF+ 先天淋巴细胞对骨髓生成的影响和 IL-17A+ 的发育最近与疼痛相关的骨髓细胞。我们的工作将揭示致病因素免疫疼痛机制并发现可用于治疗的新分子靶点治疗干预并直接造福全世界的关节炎患者。