Immune dysregulation of pemphigus in humans and mice

Tomoaki Yokoyama, Masayuki Amagai

Research output: Contribution to journalReview articlepeer-review

20 Citations (Scopus)


Pemphigus vulgaris is an autoimmune blistering disease of the skin and mucous membranes that is caused by immunoglobulin (Ig)G autoantibodies against the cadherin-type adhesion molecule desmoglein (Dsg)3 expressed on stratified epithelial cells. Interaction between antigen-specific T and B cells, which is selectively achieved through T-cell receptor/major histocompatibility complex-peptide complex association and subsequently corroborated by co-stimulatory molecules such as CD40/CD154, is required for production of pathological anti-desmoglein 3 antibody. Some genetically and environmentally susceptible individuals harbor desmoglein reactive B and T cells, and anti-desmoglein antibodies were detected in their serum. Analysis of the anti-desmoglein antibody clones derived from pemphigus patients or pemphigus model mice revealed that pathogenic antibodies mostly react with conformational epitopes on mature form desmogleins, whereas non-pathogenic ones tend to react with non-conformational epitopes. Surprisingly, antibodies to the Dsg1 precursor pro-protein are also cloned from individuals without pemphigus. These observations suggest that active suppression by regulatory cell subsets is dominant in these susceptible individuals. In fact, Dsg-reactive T-inducible regulatory type 1 (Tr1) cells are readily detected in healthy carriers of pemphigus-related human leukocyte antigen haplotypes, but rarely in pemphigus patients. These Tr1 cells can be functionally converted to T-helper 2-like cells which secrete interleukin-2 by inactivation of Foxp3 through antisense oligonucleotides. Thus, delicate balance between self-reactive lymphocytes and regulatory T cells may be a key element in determining whether individuals produce pathogenic antibodies and develop pemphigus phenotypes or not.

Original languageEnglish
Pages (from-to)205-213
Number of pages9
JournalJournal of Dermatology
Issue number3
Publication statusPublished - 2010 Mar


  • Autoantibodies
  • Autoimmunity
  • Pemphigus
  • Regulatory
  • Self-tolerance
  • T lymphocytes

ASJC Scopus subject areas

  • Dermatology


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