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Skin Resident Memory T Cell Dysfunction In The Tibia Fracture Model Of Complex Regional Pain Syndrome
Abstract   Open access   Peer reviewed

Skin Resident Memory T Cell Dysfunction In The Tibia Fracture Model Of Complex Regional Pain Syndrome

Jason Wickman, Botros Shenoda, Rachel Van Duyne, Zachary Kline and Seena Ajit
The journal of pain, v 24(4), pp 16-16
Apr 2023
DOI: https://doi.org/10.1016/j.jpain.2023.02.060
url
https://doi.org/10.1016/j.jpain.2023.02.060View
Published, Version of Record (VoR)Open Access (Publisher-Specific),  Open

Abstract

Complex regional pain syndrome (CRPS) is a debilitating chronic pain disorder that with no effective treatments. Several microRNA (miRNA) are commonly dysregulated in CRPS patient and tibia fracture model of CRPS (TFM) mice, including miR-25 which is associated with positive treatment outcomes in patients. Interestingly, these miRNAs are predicted to target several genes critical to resident memory T cell (Trm) function. We hypothesize that miRNA dysregulation contributes to the pathology of CRPS through regulation of skin Trm development and maintenance. Therapeutic strategies blocking Trm development or maintenance may be beneficial in treating this disease. Whole blood samples were obtained from CRPS patients or healthy controls. miRNA and gene expression changes in blood and T cells were assessed by qPCR. Animals were treated with therapeutic agents after development of TFM and monitored for behavioral outcomes and T cell populations of collected tissues were analyzed at different time points by flow cytometry. There was an inverse correlation of miR-25 and CD69 in blood samples from CRPS patients compared to controls. TFM hindlimb skin shows increased epidermal CD8+ and CD4+ Trm, dermal CD4+ Trm. Epidermal CD8+ Trm, dermal CD4+ Trm are marked by increases in CD103+CD49a+ populations, and along with splenic CD8+ Tem show increased CD122+ cells. Therapeutic studies are ongoing. miRNA signatures in CRPS patients and TFM mice show common alterations which are capable of regulating CD69, a core Trm marker. TFM hindlimb skin shows increased pathological Trm populations and treatments targeting Trm development and maintenance may be beneficial in treating CRPS. 1RF1NS130481-01.

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