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 language | English (US) |
|---|---|
| Pages (from-to) | 1196-1206 |
| Number of pages | 11 |
| Journal | Journal of Investigative Dermatology |
| Volume | 128 |
| Issue number | 5 |
| DOIs | |
| State | Published - Jan 1 2008 |
| Externally published | Yes |
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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 journal › Article
}
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 -