From IPEX syndrome to FOXP3 mutation: A lesson on immune dysregulation

Rosa Bacchetta, Federica Barzaghi, Maria Grazia Roncarolo

Research output: Contribution to journalArticlepeer-review


Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) syndrome is a rare disorder that increasingly has gained attention as a model of genetic autoimmunity. Numerous papers documenting the key clinical and molecular characteristics of IPEX have provided a detailed understanding of this devastating disease. IPEX is a primary immunodeficiency caused by mutations in the gene FOXP3, which encodes an essential transcription factor required for maintenance of thymus-derived regulatory T (tTreg) cells. tTreg cell dysfunction is the main pathogenic event leading to multiorgan autoimmunity in IPEX. In addition to the traditional clinical presentation (i.e., severe enteropathy, type 1 diabetes, and eczema), IPEX may encompass other variable and distinct clinical manifestations. As IPEX awareness and characterization have increased, so has identification of FOXP3 mutations, with at least 70 to date. Thus, while FOXP3 is the unifying gene, IPEX is a complex and diverse clinical continuum of disorders. Despite understanding IPEX pathogenesis, new treatment options have remained elusive, although early diagnosis led to hematopoietic stem cell transplantation (HSCT) and immunosuppression treatment and improved patient outcomes. Here, we review current knowledge about IPEX syndrome and highlight findings that could lead to novel targeted treatments.

Original languageEnglish
JournalAnnals of the New York Academy of Sciences
Publication statusAccepted/In press - 2016
Externally publishedYes


  • Autoimmune enteropathy
  • FOXP3
  • HSCT
  • IPEX
  • Neonatal diabetes
  • Primary immunodeficiency
  • T

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • History and Philosophy of Science


Dive into the research topics of 'From IPEX syndrome to FOXP3 mutation: A lesson on immune dysregulation'. Together they form a unique fingerprint.

Cite this