Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes

Marta Bertolini, Youhei Uchida, Ralf Paus

Research output: Contribution to journalReview article

9 Citations (Scopus)

Abstract

Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the - as yet elusive - key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.

Original languageEnglish (US)
Pages (from-to)9-12
Number of pages4
JournalJournal of Investigative Dermatology Symposium Proceedings
Volume17
Issue number2
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

Fingerprint

Alopecia Areata
T-Lymphocytes
Hair Follicle
Skin
Peripheral Tolerance
Antigens
Microdissection
Major Histocompatibility Complex
Research
Immunotherapy
Autoimmune Diseases
Digestion
Lasers
Epithelium
Biomarkers
Lymphocytes
Technology

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes. / Bertolini, Marta; Uchida, Youhei; Paus, Ralf.

In: Journal of Investigative Dermatology Symposium Proceedings, Vol. 17, No. 2, 01.11.2015, p. 9-12.

Research output: Contribution to journalReview article

@article{c5cf8fda66324e67b0355f2b1dc6ebff,
title = "Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes",
abstract = "Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the - as yet elusive - key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.",
author = "Marta Bertolini and Youhei Uchida and Ralf Paus",
year = "2015",
month = "11",
day = "1",
doi = "10.1038/jidsymp.2015.31",
language = "English (US)",
volume = "17",
pages = "9--12",
journal = "Journal of Investigative Dermatology Symposium Proceedings",
issn = "1087-0024",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Toward the Clonotype Analysis of Alopecia Areata-Specific, Intralesional Human CD8+ T Lymphocytes

AU - Bertolini, Marta

AU - Uchida, Youhei

AU - Paus, Ralf

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the - as yet elusive - key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.

AB - Alopecia areata (AA) is an organ-restricted autoimmune disease that mainly affects the hair follicle (HF). Several findings support a key primary effector role of CD8+ T cells in the disease pathogenesis. Autoreactive CD8+ T cells are not only present in the characteristic peribulbar inflammatory cell infiltrate of lesional AA HFs but are also found to be infiltrating in lesional HF epithelium where they are thought to recognize major histocompatibility complex class I-presented (auto-)antigens. However, the latter still remain unidentified. Therefore, one key aim in AA research is to identify the clonotypes of autoaggressive, intralesional CD8+ T cells. Therapeutically, this is important (a) so that these lymphocytes can be selectively eliminated or inhibited, (b) to identify the - as yet elusive - key (auto-)antigens in AA, and/or (c) to induce peripheral tolerance against the latter. Therefore, we have recently embarked on a National Alopecia Areata Foundation-supported project that attempts to isolate disease-specific, intralesional CD8+ T cells from AA skin in order to determine their TCR clonotype, using two complementary strategies. The first method is based on the enzymatic skin digestion from lesional AA skin, followed by either MACS technology and single-cell picking or FACS cell sorting, while the second method on laser microdissection. The identification of disease-specific TCRs can serve as a basis for specific AA immunotherapy along the lines sketched above and may possibly also provide prognostic biomarkers. If successful, this research strategy promises to permit, at long last, the causal therapy of AA.

UR - http://www.scopus.com/inward/record.url?scp=84946737142&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946737142&partnerID=8YFLogxK

U2 - 10.1038/jidsymp.2015.31

DO - 10.1038/jidsymp.2015.31

M3 - Review article

C2 - 26551936

AN - SCOPUS:84946737142

VL - 17

SP - 9

EP - 12

JO - Journal of Investigative Dermatology Symposium Proceedings

JF - Journal of Investigative Dermatology Symposium Proceedings

SN - 1087-0024

IS - 2

ER -