Evidence that the bulge region is a site of relative immune privilege in human hair follicles.
BACKGROUND
Recent gene profiling data suggest that, besides the anagen hair bulb, the epithelial stem cell region in the outer root sheath of hair follicles (HFs), termed the bulge, may also represent an area of relative immune privilege (IP).


OBJECTIVE
To investigate whether the human HF bulge is a site of relative IP within anagen VI HFs.


METHODS
Anagen VI HFs from normal human scalp skin were analysed using immunohistological staining techniques, quantitative histomorphometry and statistical analysis. For functional evidence we performed full-thickness human scalp skin organ cultures to investigate whether interferon (IFN)-gamma, a key inducer of IP collapse in hair bulbs, has a similar effect on the putative bulge IP.


RESULTS
Major histocompatibility complex (MHC) class Ia, beta(2)-microglobulin and MHC class II immunoreactivity are downregulated in the human bulge. The immunosuppressants alpha-melanocyte stimulating hormone, transforming growth factor-beta2, macrophage migration inhibitory factor and indoleamine-2,3-dioxygenase (IDO) are upregulated in the CD200+, stem cell-rich bulge region. These CD200+ cells also co-express HLA-E. Furthermore, IFN-gamma induces significant ectopic MHC class Ia expression in bulge cells of organ-cultured human scalp skin.


CONCLUSIONS
These data suggest that the bulge of human anagen HFs represents a hitherto unrecognized site of relative IP in human skin. Simultaneously, we present the first evidence of IDO and HLA-E protein expression in normal human HFs. Bulge IP presumably protects the HF epithelial stem cell reservoir from autoaggressive immune attack whereas a loss of bulge IP may play a central role in the pathogenesis of cicatricial alopecias.
Meyer
K C
KC
Department of Dermatology, Allergology and Venereology, University of Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Klatte
J E
JE
Dinh
H V
HV
Harries
M J
MJ
Reithmayer
K
K
Meyer
W
W
Sinclair
R
R
Paus
R
R
D015536:Down-Regulation / Q000276:immunology; D018859:Hair Follicle / Q000187:drug effects / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000378:metabolism; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism; D007371:Interferon-gamma / Q000276:immunology / Q000494:pharmacology*; D012535:Scalp / Q000276:immunology; D001613:beta 2-Microglobulin / Q000378:metabolism
D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D007166:Immunosuppressive Agents; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D001613:beta 2-Microglobulin; D007371:Interferon-gamma