Jung Min Park1,2,3,4, Mee Sook Jun1,2, Jung-A Kim5,6, Nanda Maya Mali1,2, Tsai-Ching Hsi7, Areum Cho1, Jung Chul Kim5,6, Jun Young Kim8, Incheol Seo9, Jungmin Kim3, Moonkyu Kim10,11, Ji Won Oh12,13,14,15. 1. Department of Anatomy, Kyungpook National University School of Medicine, Daegu, Korea. 2. Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea. 3. Department of Microbiology, Kyungpook National University School of Medicine, Daegu, Korea. 4. Immune Square Inc., Daegu, Korea. 5. Department of Immunology, Kyungpook National University School of Medicine, Daegu, Korea. 6. Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea. 7. Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. 8. Department of Dermatology, School of Medicine, Kyungpook National University, Daegu, Korea. 9. Department of Microbiology, Dongguk University College of Medicine, Gyeongju, Korea. 10. Department of Immunology, Kyungpook National University School of Medicine, Daegu, Korea. moonkim@knu.ac.kr. 11. Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea. moonkim@knu.ac.kr. 12. Department of Anatomy, Kyungpook National University School of Medicine, Daegu, Korea. ohjiwon@knu.ac.kr. 13. Biomedical Research Institute, Kyungpook National University Hospital, Daegu, Korea. ohjiwon@knu.ac.kr. 14. Immune Square Inc., Daegu, Korea. ohjiwon@knu.ac.kr. 15. Hair Transplantation Center, Kyungpook National University Hospital, Daegu, Korea. ohjiwon@knu.ac.kr.
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.
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.
Authors: Toru Fukushima; Shu-ichi Matsuzawa; Christina L Kress; Jean Marie Bruey; Maryla Krajewska; Sophie Lefebvre; Juan M Zapata; Ze'ev Ronai; John C Reed Journal: Proc Natl Acad Sci U S A Date: 2007-04-02 Impact factor: 11.205