title: Collapse and restoration of MHC class-I-dependent immune privilege: exploiting the human hair follicle as a model.
abstract: The collapse of major histocompatibility complex (MHC) class-I-dependent immune privilege can lead to autoimmune disease or fetal rejection. Pragmatic and instructive models are needed to clarify the as yet obscure controls of MHC class I down-regulation in situ, to dissect the principles of immune privilege generation, maintenance, and collapse as well as to develop more effective strategies for immune privilege restoration. Here, we propose that human scalp hair follicles, which are abundantly available and easily studied, are ideally suited for this purpose: interferon-gamma induces ectopic MHC class I expression in the constitutively MHC class-I-negative hair matrix epithelium of organ-cultured anagen hair bulbs, likely via interferon regulatory factor-1, along with up-regulation of the MHC class I pathway molecules beta(2)microglobulin and transporter associated with antigen processing (TAP-2). In the first report to identify natural immunomodulators capable of down-regulating MHC class I expression in situ in a normal, neuroectoderm-derived human tissue, we show that ectopic MHC class I expression in human anagen hair bulbs can be normalized by treatment with alpha-MSH, IGF-1, or TGF-beta1, all of which are locally generated, as well as by FK506. These agents are promising candidates for immune privilege restoration and for suppressing MHC class I expression where this is clinically desired (eg, in alopecia areata, multiple sclerosis, autoimmune uveitis, mumps orchitis, and fetal or allograft rejection).
authors.affiliation: Department of Dermatology, University Hospital Hamburg-Eppendorf, University of Hamburg, Hamburg, Germany.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Ito
authors.forename: Natsuho
authors.initials: N
authors.lastname: Ito
authors.forename: Albrecht
authors.initials: A
authors.lastname: Bettermann
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Tokura
authors.forename: Masahiro
authors.initials: M
authors.lastname: Takigawa
authors.forename: Ralf
authors.initials: R
authors.lastname: Paus
mesh_terms: D015536:Down-Regulation / Q000187:drug effects; D018859:Hair Follicle / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology; D017403:In Situ Hybridization; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D018448:Models, Immunological; D009924:Organ Culture Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012535:Scalp / Q000187:drug effects / Q000276:immunology; D016559:Tacrolimus / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D015395:Histocompatibility Antigens Class I; D007166:Immunosuppressive Agents; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D000521:alpha-MSH; D007334:Insulin-Like Growth Factor I; D016559:Tacrolimus