Evidence that the bulge region is a site of relative immune privilege in human hair follicles

K. C. Meyer, J. E. Klatte, H. V. Dinh, M. J. Harries, K. Reithmayer, W. Meyer, R. Sinclair, Ralf Paus

Research output: Contribution to journalArticle

107 Citations (Scopus)

Abstract

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). Objectives: 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)-γ, 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, β2-microglobulin and MHC class II immunoreactivity are downregulated in the human bulge. The immunosuppressants α-melanocyte stimulating hormone, transforming growth factor-β2, 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-γ 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.

Original languageEnglish (US)
Pages (from-to)1077-1085
Number of pages9
JournalBritish Journal of Dermatology
Volume159
Issue number5
DOIs
StatePublished - Nov 1 2008
Externally publishedYes

Fingerprint

Hair Follicle
Major Histocompatibility Complex
Scalp
Indoleamine-Pyrrole 2,3,-Dioxygenase
Skin
Stem Cells
Hair
Interferons
Epithelial Cells
Macrophage Migration-Inhibitory Factors
Melanocyte-Stimulating Hormones
Organ Culture Techniques
Alopecia
Transforming Growth Factors
Immunosuppressive Agents
Cultured Cells
Down-Regulation
Staining and Labeling

Keywords

  • Bulge
  • HLA-E
  • Human hair follicles
  • Immune privilege
  • Indoleamine-2,3- dioxygenase
  • Macrophage migration inhibitory factor

ASJC Scopus subject areas

  • Dermatology

Cite this

Evidence that the bulge region is a site of relative immune privilege in human hair follicles. / Meyer, K. C.; Klatte, J. E.; Dinh, H. V.; Harries, M. J.; Reithmayer, K.; Meyer, W.; Sinclair, R.; Paus, Ralf.

In: British Journal of Dermatology, Vol. 159, No. 5, 01.11.2008, p. 1077-1085.

Research output: Contribution to journalArticle

Meyer, KC, Klatte, JE, Dinh, HV, Harries, MJ, Reithmayer, K, Meyer, W, Sinclair, R & Paus, R 2008, 'Evidence that the bulge region is a site of relative immune privilege in human hair follicles', British Journal of Dermatology, vol. 159, no. 5, pp. 1077-1085. https://doi.org/10.1111/j.1365-2133.2008.08818.x
Meyer, K. C. ; Klatte, J. E. ; Dinh, H. V. ; Harries, M. J. ; Reithmayer, K. ; Meyer, W. ; Sinclair, R. ; Paus, Ralf. / Evidence that the bulge region is a site of relative immune privilege in human hair follicles. In: British Journal of Dermatology. 2008 ; Vol. 159, No. 5. pp. 1077-1085.
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AU - Meyer, K. C.

AU - Klatte, J. E.

AU - Dinh, H. V.

AU - Harries, M. J.

AU - Reithmayer, K.

AU - Meyer, W.

AU - Sinclair, R.

AU - Paus, Ralf

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N2 - 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). Objectives: 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)-γ, 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, β2-microglobulin and MHC class II immunoreactivity are downregulated in the human bulge. The immunosuppressants α-melanocyte stimulating hormone, transforming growth factor-β2, 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-γ 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.

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