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

• 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
• 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

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.

项目总结/摘要 IL-23/IL-17轴与许多自身免疫性和自身炎性疾病有关，包括 银屑病性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。 我们一直在研究IL-23/IL-17轴在炎症性关节炎通过NIH奖 R 01 AR 062173，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-10的免疫机制。 作为特别关注通知（NOSI）一部分的17轴疼痛：NOT-AR-23-015紧急 竞争性修订，以增加研究前沿疼痛研究风湿，皮肤， 肌肉骨骼疾病。具体来说，这种补充将解决细胞和分子 负责疼痛的机制。因此，我们将调整动物模型， 结合我们的合作者提供的疼痛读数，我们将识别效应器， 在炎症性关节炎中介导免疫疼痛的传感器。我们的两个具体目标将解决 通过GM-CSF+先天淋巴样细胞的骨髓生成作用和IL-17 A+的发展 最近与疼痛有关的骨髓细胞。我们的工作将揭示致病的 免疫疼痛的机制，并发现新的分子靶点，可用于 治疗干预和直接受益关节炎患者在世界各地。