Targeting Regulatory T Cells to Treat Chronic Migraine and Post-Traumatic Headache
Abstract
In this study we propose test the hypothesis that that reduced regulation of immune homeostasis by regulatory T (Treg) cells at peripheral tissues contributes to the chronification of headache and cognitive impairment in chronic migraine (CM) and post-traumatic headache (PTH). The research objective is to validate Treg as a cellular target for novel, peripherally active therapy for CM and PTH, with mechanisms distinct from the existing treatment options. We made significant progress during the last funding period. First, we are on track of establishing breeding colonies for the transgenic mice to be used in Specific Aims 1 and 2. Secondly, we have established the methodology of profiling time-dependent changes of immune cells by mTBI in the peripheral blood to be used in Specific Aims 1A and 3A. Lastly, we have investigated the molecular mechanisms underlying the therapeutic effects of low-dose interleukin-2 (ld-IL2) and Treg cells onCM-related behavioral and neuronal sensitization. Our results not only indicate that ld-IL2 and Treg cells engage both peripheral IL-10 and TGFbeta signaling pathways to reverse CM-related sensitizations, but also suggest that the IL-10 and TGFbeta1 signaling pathways in trigeminal ganglion neurons are potential targets for CM therapy. Similar strategy will be used in Specific Aim 2B to elucidate the mechanisms through which ld-IL2 reverses mTBI-induced behavioral and neuronal changes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2022
- Accession Number
- AD1190554
Entities
People
- Yu-qing Cao
Organizations
- Washington University in St. Louis