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

项目摘要/摘要 IL-23/IL-17轴与许多自身免疫性和自身炎症性疾病有关，包括 银屑病关节炎是一种与牛皮癣密切相关的慢性进行性炎症性关节炎。 我们通过美国国立卫生研究院奖一直在研究炎症性关节炎中的IL-23/IL-17轴 R01AR062173，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-2的免疫机制。 17作为特别关注通知(NOSI)的一部分的疼痛轴心：NOT-AR-23-015紧急 竞争性修订以增加风湿性、皮肤病和其他疾病的刀刃疼痛研究 肌肉骨骼疾病。具体地说，这份补充材料将涉及细胞和分子 导致疼痛的机制。因此，我们将调整动物模型，并在 结合我们的合作者协助的疼痛读数，我们将识别效应器和 炎症性关节炎中介导免疫疼痛的转导分子。我们的两个具体目标将解决 粒-巨噬细胞集落刺激因子诱导的骨髓生成及IL-17A的产生 最近被认为与疼痛有关的髓系细胞。我们的工作将揭开病原体 免疫性疼痛的机制和发现可用于治疗的新分子靶点 治疗干预和直接惠及世界各地的关节炎患者。

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.