Role of Autophagy in Alopecia Areata

Year: 
2019
PI Name: 
Rupali Gund, PhD
Type:
Mentored Investigator Award
Status: 
Active

Summary

This project aims to understand the role of autophagy (a normal physiological process in the body that deals with destruction of cells in the body) in normal hair cycling and its role in the development of alopecia areata in the C3H/HeJ mouse model.

Abstract

Alopecia Areata (AA) is an organ-restricted autoimmune disease that specifically attacks the hair follicles, resulting in well-demarcated (AA Patchy) or diffuse non-scarring hair loss of the scalp (AA Totalis) or the entire body (AA Universalis). AA is a highly prevalent disease with a lifetime risk of 2.1%, however, the underlying disease mechanisms remain incompletely defined and under-studied. Histologically, AA presents as a “swarm of bees” in which inflammatory T lymphocytes attack the pigmented actively growing hair follicles. The prevalent notion for disease is thought to be the loss of immune privilege of hair follicles causing abnormal activation of pathogenic T cells. Genetic association studies previously conducted in our lab found several autophagy related genes associated with AA. In addition, our gene expression analysis revealed altered expression of autophagy related genes, prompting us to hypothesize that dysregulation of autophagy plays a critical role in AA pathogenesis. Autophagy is a survivalpromoting mechanism that involves capturing, degradation, and recycling of intracellular proteins and organelles in lysosomes. However, the contribution of autophagy in loss of hair follicle immune privilege and development of AA is not characterized. This project aims to understand the role of autophagy in normal hair cycling and its contribution to the development of alopecia in grafted C3H/HeJ mouse model.

Impact

If successful, this study could provide new insights into the mechanism of alopecia areata pathogenesis mediated by autophagy and also identify novel targets for therapeutic intervention.