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.
authors.affiliation: Department of Dermatology, Hamamatsu University School of Medicine, Hamamatsu, Japan. itoutai@hama-med.ac.jp
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Natsuho
authors.initials: N
authors.lastname: Ito
authors.forename: Matthias
authors.initials: M
authors.lastname: Saatoff
authors.forename: Hideo
authors.initials: H
authors.lastname: Hashizume
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Fukamizu
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Nickoloff
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D000293:Adolescent; D000328:Adult; D000506:Alopecia Areata / Q000276:immunology* / Q000473:pathology*; D015704:CD4 Antigens / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D016827:CD8 Antigens / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D018859:Hair Follicle / Q000276:immunology* / Q000473:pathology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology*; D007371:Interferon-gamma / Q000494:pharmacology; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism; D008875:Middle Aged; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic / Q000378:metabolism; D054343:Receptors, KIR2DL2 / Q000378:metabolism; D054344:Receptors, KIR2DL3 / Q000378:metabolism; D055607:Receptors, Natural Killer Cell; D012535:Scalp / Q000276:immunology / Q000473:pathology
chemical_list: D015704:CD4 Antigens; D019002:CD56 Antigen; D016827:CD8 Antigens; D015395:Histocompatibility Antigens Class I; C515077:KIR2DL2 protein, human; C515078:KIR2DL3 protein, human; C527059:KLRC2 protein, human; C527085:KLRK1 protein, human; C099187:MHC class I-related chain A; D008263:Macrophage Migration-Inhibitory Factors; D055654:NK Cell Lectin-Like Receptor Subfamily C; D055655:NK Cell Lectin-Like Receptor Subfamily K; D011971:Receptors, Immunologic; D054343:Receptors, KIR2DL2; D054344:Receptors, KIR2DL3; D055607:Receptors, Natural Killer Cell; D007371:Interferon-gamma; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human