Frontiers in alopecia areata pathobiology research

Amos Gilhar, Rimma Laufer-Britva, Aviad Keren, Ralf Paus

Research output: Contribution to journalReview articlepeer-review

8 Scopus citations


This current review explores selected and as yet insufficiently investigated frontiers in current alopecia areata (AA) pathobiology research, with an emphasis on potential “new” players in AA pathobiology that deserve more systematic exploration and therapeutic targeting. Indeed, new evidence suggests that CD8+ T cells, which have long been thought to be the central players in AA pathobiology, are not the only drivers of disease. Instead, subsets of natural killer (NK) and so-called “unconventional” T cells (invariant NK T cells, γδ T cells, classic NK cells, and type 1 innate lymphoid cells), all of which can produce large amounts of IFN-γ, might also drive AA pathobiology independent of classical, autoantigen-dependent CD8+ T-cell functions. Another important new frontier is the role of regulatory lymphocyte subsets, such as regulatory T cells, γδ regulatory T cells, NKT10 cells, and perifollicular mast cells, in maintaining physiologic hair follicle immune privilege (IP); the extent to which these functions are defective in patients with AA; and how this IP-protective role could be restored therapeutically in patients with established AA. Broadening our AA research horizon along the lines suggested above promises not only to open the door to innovative and even more effective immunotherapy strategies for AA but will also likely be relevant for other autoimmune disorders in which pathobiology, ectopic MHC class I expression, and IP collapse play an important role.

Original languageEnglish (US)
Pages (from-to)1478-1489
Number of pages12
JournalJournal of Allergy and Clinical Immunology
Issue number6
StatePublished - Dec 2019


  • Autoantigens
  • IFN-γ
  • invariant natural killer T cell 10
  • regulatory T cells
  • severe combined immune deficiency mice

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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