Immunology of the human nail apparatus: The nail matrix is a site of relative immune privilege

Taisuke Ito, Natsuho Ito, Matthias Saathoff, Barbara Stampachiacchiere, Albrecht Bettermann, Sylvia Bulfone-Paus, Masahiro Takigawa, Brian J. Nickoloff, Ralf Paus

Research output: Contribution to journalArticlepeer-review

103 Scopus citations


The nail apparatus is constantly exposed to environmental damage. It requires effective immune responses to combat infection, while avoiding the loss of nail production and regeneration by autoaggressive immunity. By immunohistology, we define here previously unknown characteristics of the normal human nail immune system (NIS). Compared with other regions of nail epithelium, human leukocyte antigen (HLA)-A/B/C expression is prominently downregulated on both keratinocytes and melanocytes of the proximal nail matrix (PNM), whereas HLA-G+ is upregulated here. Together with the expression of macrophage migration inhibitory factor in PNM, this may serve to inhibit an natural killer (NK) cell attack on major histocompatibility complex (MHC) class la-negative PNM. PNM also displays strong immunoreactivity for potent, locally generated immunosuppressants such as transforming growth factor-β1, α-melanocyte stimulating hormone, insulin-like growth factor-1, and adrenocorticotropic hormone, exhibits unusually few CD1a+, CD4 +, or CD8+, NK, and mast cells. Finally, MHC class II and CD209 expression on CD1a+ cells in and around the PNM is reduced, indicating diminished antigen-presenting capacity. Thus, the NIS strikingly differs from the skin immune system, but shows intriguing similarities to the hair follicle immune system, including the establishment of an area of relative immune privilege in the PNM. This nail immune privilege may offer a relative safeguard against autoimmunity. But, the localized intraepithelial defect of innate and adaptive immunity in the PNM revealed here also may impede effective anti-infection defense.

Original languageEnglish (US)
Pages (from-to)1139-1148
Number of pages10
JournalJournal of Investigative Dermatology
Issue number6
StatePublished - Dec 2005
Externally publishedYes


  • CD1a
  • HLA-G
  • Immune privilege
  • MHC class I
  • MICA
  • MIF
  • NK cell
  • Nail
  • TGF-β1
  • α-MSH

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology


Dive into the research topics of 'Immunology of the human nail apparatus: The nail matrix is a site of relative immune privilege'. Together they form a unique fingerprint.

Cite this