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KMID : 1377020220190010105
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Tissue Engineering and Regenerative Medicine
2022 Volume.19 No. 1 p.105 ~ p.116
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Restoration of Immune Privilege in Human Dermal Papillae Controlling Epithelial-Mesenchymal Interactions in Hair Formation
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Park Jung-Min
Jun Mee-Sook
Kim Jung-A.
Mali Nanda Maya
Hsi Tsai-Ching
Cho A-Reum
Kim Jung-Chul
Kim Jun-Young
Seo In-Cheol
Kim Jung-Min
Kim Moon-Kyu
Oh Ji-Won
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Abstract
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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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KEYWORD
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Immune privilege, Hair follicle, MHC molecule, Epithelial-mesenchymal interaction
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