The role of hair follicle immune privilege collapse in alopecia areata: status and perspectives

J Investig Dermatol Symp Proc. 2013 Dec;16(1):S25-7. doi: 10.1038/jidsymp.2013.7.


Alopecia areata (AA) may represent a CD8+T cell-mediated, organ-specific autoimmune disease in which as yet elusive autoantigens are recognized, once they become exposed by ectopic major histocompatibility complex class I expression by anagen hair follicles (HFs) that have lost their relative immune privilege (IP). On this basis, AA research is chiefly challenged with identifying the autoreactive CD8+T cells and their cognate autoantigens as well as key inducers of HF-IP collapse and "HF-IP guardians" that prevent and/or can restore IP collapse. However, natural killer group 2D-positive (NKG2D+) cells (incl. NK, NKT, and CD8+T cells) and NKG2D-activating ligands from the MICA (MHC I-related chain A) family may also have a key role in AA pathogenesis, as a massive infiltrate of IFN-γ-secreting NKG2D+ cells alone suffices to induce the AA phenotype. Therefore, we speculate that AA may represent a stereotypic, but distinct HF response pattern to inflammatory insults associated with HF-IP collapse.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alopecia Areata / immunology*
  • Animals
  • Autoantigens / immunology
  • Autoimmune Diseases / immunology*
  • CD8-Positive T-Lymphocytes
  • GPI-Linked Proteins / immunology
  • Hair Follicle / immunology*
  • Humans
  • Intercellular Signaling Peptides and Proteins / immunology
  • Killer Cells, Natural / chemistry
  • Killer Cells, Natural / immunology
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily K / analysis
  • Self Tolerance / immunology*


  • Autoantigens
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • ULBP2 protein, human