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

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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.