A Novel Treg Augmenting Therapy for Patients with Alopecia Areata
This project will examine the function of regulatory T cells (Tregs) in the activation and differentiation of hair follicle stem cells in alopecia areata and determine whether the activity of Tregs can be modulated in alopecia areata using a novel IL-2 molecule.
Regulatory T cells (Tregs) play a major role in establishing and maintaining immune homeostasis. We have discovered that both murine and human skin contain a unique population of Tregs that preferentially localize to hair follicles (HFs) and that these cells are required for HF regeneration as well as proper HF cycling. In addition, we have found that Tregs mediate these effects by promoting the activation and differentiation of hair follicle stem cells (HFSCs). The underlying theme of this proposal is to provide the cellular and molecular foundation for Treg augmentation therapy to treat patients with alopecia areata (AA). To achieve this goal, we will assess whether augmenting Tregs in mice results in enhanced HFSC function and HF cycling/regeneration. In addition, using cutting-edge CyTOF technology, we will comprehensively quantify the immune cell subsets infiltrating AA skin. In final experiments, we will attempt to augment Tregs in single cell suspensions derived from lesional AA skin and Treg activation quantified relative to other immune cell subsets. Given that AA is defined by both a dysfunction in HF regeneration and a defect in Tregs, our results may have direct implications for patients suffering from this disease.
If successful, this study may help pave the way for future clinical trials testing the safety and efficacy of regulatory T cell (Treg) augmenting therapies in patients with alopecia areata.