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

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.

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Acknowledgement

This work was supported by Biomedical Research Institute Grant, Kyungpook National University Hospital (2016).

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Authors

Contributions

MK and JWO developed the concepts, designed the experimental methodology, analyzed the data, wrote, reviewed, and approved the final draft. JMP, MSJ, IS and JAK conducted the experiments, analyzed the data, wrote, and edited a draft under supervision of MK and JWO. NMM, TCH, AC, JCK, JYK and JK conducted the experiments and reviewed the draft. MK and JWO supervised the study.

Corresponding authors

Correspondence to Moonkyu Kim or Ji Won Oh.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethical statement

The study protocol was approved by the institutional review board of Kyungpook National University, School of Medicine (IRB No. KNU 2013–01-037–004).

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Supplementary Information

Below is the link to the electronic supplementary material.

13770_2021_392_MOESM1_ESM.tif

Supplementary file 1: Fig. S1. The expression pattern of CD8 + cells in nine AA patient. The comparison in different stage with H&E staining and IHC in AA patients.

13770_2021_392_MOESM2_ESM.xlsx

Supplementary file 2: Table S1. The total gene list of the DEGs analyzed from MHC class I+ stem cell. The GEO data sets (GSE 11089) was used to select DEGs.

13770_2021_392_MOESM3_ESM.xlsx

Supplementary file 3: Table S2. The terms of gene function used in the bubble chart. The bubble chart visualized biological functions of up-regulated genes and down-regulated genes.

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Park, J.M., Jun, M.S., Kim, JA. et al. Restoration of Immune Privilege in Human Dermal Papillae Controlling Epithelial-Mesenchymal Interactions in Hair Formation. Tissue Eng Regen Med (2021). https://doi.org/10.1007/s13770-021-00392-7

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Keywords

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