The immunological and genetic basis of immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome

Curr Opin Allergy Clin Immunol. 2015 Dec;15(6):525-32. doi: 10.1097/ACI.0000000000000214.

Abstract

Purpose of review: This article presents a comprehensive review of the immunodysregulation, polyendocrinopathy, enteropathy and X-linked (IPEX) syndrome, covering both the clinical and molecular aspects of the disease. (Figure is included in full-text article.)

Recent findings: The IPEX syndrome is a rare immunological disorder in humans caused by inheritable mutations in the FOXP3 gene, the master transcriptional regulator for the development and function of CD4 regulatory T (Treg) cells. Forkhead box protein 3 (FOXP3) Treg cells represent a unique T-cell lineage with inhibitory functions, and are responsible for immune homeostasis and tolerance to self and nonself antigens. Evidence shows that a Treg developmental deficiency or dysfunction underlies the severe, multiorgan, autoimmune disease of IPEX.

Summary: An in-depth structural and functional analysis of the molecular domains of FOXP3 is essential for our understanding of the observed clinical heterogeneity and prognosis in IPEX.

Publication types

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

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Lineage
  • Diabetes Mellitus, Type 1 / congenital*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 1 / immunology
  • Diarrhea / genetics
  • Diarrhea / immunology*
  • Forkhead Transcription Factors / genetics
  • Forkhead Transcription Factors / metabolism*
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / immunology*
  • Homeostasis
  • Humans
  • Immune System Diseases / congenital*
  • Immune System Diseases / genetics
  • Immune System Diseases / immunology
  • Mutation / genetics
  • Self Tolerance
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • FOXP3 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Immune Dysregulation, Polyendocrinopathy, Enteropathy, X-Linked Syndrome