Journal article
High-throughput T cell receptor sequencing identifies clonally expanded CD8+ T cell populations in alopecia areata
JCI insight, Vol.3(19), e121949
10/04/2018
DOI: 10.1172/jci.insight.121949
PMCID: PMC6237451
PMID: 30282836
Abstract
Alopecia areata (AA) is an autoimmune disease in which cytotoxic T cells specifically target growing hair follicles. We used high-throughput TCR sequencing in the C3H/HeJ mouse model of AA and in human AA patients to gain insight into pathogenic T cell populations and their dynamics, which revealed clonal CD8
+
T cell expansions in lesional skin. In the C3H/HeJ model, we observed interindividual sharing of TCRβ chain protein sequences, which strongly supports a model of antigenic drive in AA. The overlap between the lesional TCR repertoire and a population of CD8
+
NKG2D
+
T cells in skin-draining lymph nodes identified this subset as pathogenic effectors. In AA patients, treatment with the oral JAK inhibitor tofacitinib resulted in a decrease in clonally expanded CD8
+
T cells in the scalp but also revealed that many expanded lesional T cell clones do not completely disappear from either skin or blood during treatment with tofacitinib, which may explain in part the relapse of disease after stopping treatment.
Analysis of the T cell repertoire in the autoimmune disease alopecia areata provides insights in antigenic drive and the response of expanded T cell clones to JAK inhibitor treatment.
Details
- Title: Subtitle
- High-throughput T cell receptor sequencing identifies clonally expanded CD8+ T cell populations in alopecia areata
- Creators
- Annemieke de Jong - University of Colorado DenverAli Jabbari - University of Colorado DenverZhenpeng Dai - University of Colorado DenverLuzhou Xing - Columbia UniversityDustin Lee - University of Colorado DenverMei Mei Li - University of Colorado DenverMadeleine Duvic - The University of Texas MD Anderson Cancer CenterMaria Hordinsky - University of MinnesotaDavid A. Norris - University of DenverVera Price - University of California, San FranciscoJulian Mackay-Wiggan - University of Colorado DenverRaphael Clynes - University of Colorado DenverAngela M. Christiano - Columbia University
- Resource Type
- Journal article
- Publication Details
- JCI insight, Vol.3(19), e121949
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/jci.insight.121949
- PMID
- 30282836
- PMCID
- PMC6237451
- ISSN
- 2379-3708
- eISSN
- 2379-3708
- Grant note
- R01AR056016,R21AR061881,P30AR069632,K01 AR068475,K08 AR069111,S10OD020056 / NIH
- Language
- English
- Date published
- 10/04/2018
- Academic Unit
- Dermatology
- Record Identifier
- 9984296306402771
Metrics
9 Record Views