Identifying pathogenic T cell receptor sequences in alopecia areata

Year: 
2015
PI Name: 
Annemieke de Jong, PhD
Type:
Bridge Grant
Status: 
Complete

Summary

This project aims to determine the T cell receptors of hair follicle infiltrating T cells and to determine their frequency in affected skin, unaffected skin and if they are circulating in the blood.

Abstract

It is known that certain white blood cells, called T cells, play an important role in the development of alopecia areata (AA). T cells infiltrate the hair follicles in AA, and have been confirmed in mouse models to be both necessary and sufficient to cause the disease. During T cell development, each T cell rearranges its genetic material in order to express a unique T cell receptor. Because this receptor is unique, the T cell receptor (TCR) can be considered a barcode by which a T cell can be identified. Recent developments in high throughput sequencing techniques have now made it possible to sequence millions of TCRs in a single skin tissue or blood sample. In contrast to other autoimmune diseases, AA is an autoimmune disease in which the target organ, the hair follicle, can be accessed during the disease process. This unique feature allows us to determine the TCR repertoire during an ongoing hair follicle attack. We propose to determine the TCRs of hair follicle infiltrating T cells, and determine their frequency in affected skin, unaffected skin and if they are circulating in the blood. The goal is to identify TCR sequences that are associated with disease in a particular patient, and determine if the circulating frequencies of the pathogenic TCRs are associated with the clinical course of the disease. Additionally, we will use the TCR sequences to identify in which T cell subset the pathogenic T cells are found. This will teach us more about the disease process and will potentially provide a biomarker for the disease.

Impact

This study utilizes Next-Gen technology for DNA sequencing to learn about disease process and potentially establish a biomarker. If successful, findings could be applied to other autoimmune diseases.

Publication

de Jong A, Jabbari A, Dai Z, Xing L, Lee D, Li MM, et al. High-throughput T cell receptor sequencing identifies clonally expanded CD8+ T cell populations in alopecia areata. JCI Insight. 2018 Oct;3(19):e121949. doi: 10.1172/jci.insight.121949.