Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack

Taisuke Ito, Natsuho Ito, Matthias Saatoff, Hideo Hashizume, Hidekazu Fukamizu, Brian J. Nickoloff, Masahiro Takigawa, Ralf Paus

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56+/NKG2D+ NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56+/NKG2D+ NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56+ NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management.

Original languageEnglish (US)
Pages (from-to)1196-1206
Number of pages11
JournalJournal of Investigative Dermatology
Volume128
Issue number5
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

Fingerprint

Hair Follicle
Alopecia Areata
Natural Killer Cells
NK Cell Lectin-Like Receptor Subfamily K
Maintenance
Macrophage Migration-Inhibitory Factors
Defects
Flow cytometry
Immunosuppressive Agents
Blood
Agglomeration
Genes
Major Histocompatibility Complex
NK Cell Lectin-Like Receptor Subfamily C
Autoimmune Diseases
Flow Cytometry
Down-Regulation
Epithelium

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. / Ito, Taisuke; Ito, Natsuho; Saatoff, Matthias; Hashizume, Hideo; Fukamizu, Hidekazu; Nickoloff, Brian J.; Takigawa, Masahiro; Paus, Ralf.

In: Journal of Investigative Dermatology, Vol. 128, No. 5, 01.01.2008, p. 1196-1206.

Research output: Contribution to journalArticle

Ito, T, Ito, N, Saatoff, M, Hashizume, H, Fukamizu, H, Nickoloff, BJ, Takigawa, M & Paus, R 2008, 'Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack', Journal of Investigative Dermatology, vol. 128, no. 5, pp. 1196-1206. https://doi.org/10.1038/sj.jid.5701183
Ito, Taisuke ; Ito, Natsuho ; Saatoff, Matthias ; Hashizume, Hideo ; Fukamizu, Hidekazu ; Nickoloff, Brian J. ; Takigawa, Masahiro ; Paus, Ralf. / Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack. In: Journal of Investigative Dermatology. 2008 ; Vol. 128, No. 5. pp. 1196-1206.
@article{1f7d57721233496798ca245b3a8c9cd0,
title = "Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack",
abstract = "Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56+/NKG2D+ NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56+/NKG2D+ NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56+ NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management.",
author = "Taisuke Ito and Natsuho Ito and Matthias Saatoff and Hideo Hashizume and Hidekazu Fukamizu and Nickoloff, {Brian J.} and Masahiro Takigawa and Ralf Paus",
year = "2008",
month = "1",
day = "1",
doi = "10.1038/sj.jid.5701183",
language = "English (US)",
volume = "128",
pages = "1196--1206",
journal = "Journal of Investigative Dermatology",
issn = "0022-202X",
publisher = "Nature Publishing Group",
number = "5",

}

TY - JOUR

T1 - Maintenance of hair follicle immune privilege is linked to prevention of NK cell attack

AU - Ito, Taisuke

AU - Ito, Natsuho

AU - Saatoff, Matthias

AU - Hashizume, Hideo

AU - Fukamizu, Hidekazu

AU - Nickoloff, Brian J.

AU - Takigawa, Masahiro

AU - Paus, Ralf

PY - 2008/1/1

Y1 - 2008/1/1

N2 - Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56+/NKG2D+ NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56+/NKG2D+ NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56+ NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management.

AB - Hair follicles (HFs) enjoy a relative immune privilege (IP) that is characterized by downregulation of major histocompatibility complex (MHC) class I and local expression of potent immunosuppressants. Normally, natural killer (NK) cells attack cells with absent/low MHC class I expression. However, because few perifollicular NK cells are found around healthy human anagen HFs, we asked how HFs escape from NK cell attack. This study suggests that this happens via an active NK cell suppression. Alopecia areata (AA), an organ-specific autoimmune disease thought to result from a collapse of HF-IP, in contrast, shows striking defects in NK cell inhibition/containment. We show that the NK cell inhibitor macrophage migration inhibitory factor is strongly expressed by the HF epithelium, and very few CD56+/NKG2D+ NK cells are observed in and around normal anagen HFs compared to AA with prominent aggregations of CD56+/NKG2D+ NK around AA-HFs. By flow cytometry, many fewer NK function-activating receptors (NKG2D, NKG2C) and significantly more killer cell Ig-like receptors-2D2/2D3 were found to be expressed on peripheral blood CD56+ NK cells of healthy controls than on those of AA patients. In addition, only weak immunoreactivity for MHC class I chain-related A gene was observed in normal anagen HFs compared to AA. To our knowledge, this defect is previously unreported and must be taken into account in AA pathogenesis and its management.

UR - http://www.scopus.com/inward/record.url?scp=42149108570&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42149108570&partnerID=8YFLogxK

U2 - 10.1038/sj.jid.5701183

DO - 10.1038/sj.jid.5701183

M3 - Article

C2 - 18160967

AN - SCOPUS:42149108570

VL - 128

SP - 1196

EP - 1206

JO - Journal of Investigative Dermatology

JF - Journal of Investigative Dermatology

SN - 0022-202X

IS - 5

ER -