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

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

Affiliations
  • 1Department of Anatomy, Kyungpook National University School of Medicine, Daegu, Korea
  • 2Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea
  • 3Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea
  • 4Immune Square Inc., Daegu, Korea
  • 5Department of Immunology, Kyungpook National University School of Medicine, Daegu, Korea
  • 6Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea
  • 7Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA
  • 8Department of Dermatology, School of Medicine, Kyungpook National University, Daegu, Korea
  • 9Department of Microbiology, Dongguk University College of Medicine, Gyeongju, Korea

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.

Keyword

Immune privilege; Hair follicle; MHC molecule; Epithelial-mesenchymal interaction
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