Restoration of Immune Privilege in Human Dermal Papillae Controlling Epithelial-Mesenchymal Interactions in Hair Formation

Tissue Eng Regen Med. 2022 Feb;19(1):105-116. doi: 10.1007/s13770-021-00392-7. Epub 2021 Oct 9.

Abstract

Background: Hair follicles are among a handful of organs that exhibit immune privilege. Dysfunction of the hair follicle immune system underlies the development of inflammatory diseases, such as alopecia areata.

Methods: Quantitative reverse transcription PCR and immunostaining was used to confirm the expression of major histocompatibility complex class I in human dermal papilla cells. Through transcriptomic analyses of human keratinocyte stem cells, major histocompatibility complex class I was identified as differentially expressed genes. Organ culture and patch assay were performed to assess the ability of WNT3a conditioned media to rescue immune privilege. Lastly, CD8+ T cells were detected near the hair bulb in alopecia areata patients through immunohistochemistry.

Results: Inflammatory factors such as tumor necrosis factor alpha and interferon gamma were verified to induce the expression of major histocompatibility complex class I proteins in dermal papilla cells. Additionally, loss of immune privilege of hair follicles was rescued following treatment with conditioned media from outer root sheath cells. Transcriptomic analyses found 58 up-regulated genes and 183 down-regulated genes related in MHC class I+ cells. Using newborn hair patch assay, we demonstrated that WNT3a conditioned media with epidermal growth factor can restore hair growth. In alopecia areata patients, CD8+ T cells were increased during the transition from mid-anagen to late catagen.

Conclusion: Identification of mechanisms governing epithelial and mesenchymal interactions of the hair follicle facilitates an improved understanding of the regulation of hair follicle immune privilege.

Keywords: Epithelial-mesenchymal interaction; Hair follicle; Immune privilege; MHC molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alopecia Areata* / metabolism
  • Alopecia Areata* / therapy
  • Epidermal Growth Factor / metabolism
  • Hair Follicle / metabolism
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / metabolism
  • Humans
  • Immune Privilege*
  • Infant, Newborn

Substances

  • Histocompatibility Antigens Class I
  • Epidermal Growth Factor