title: CD25 deficiency causes an immune dysregulation, polyendocrinopathy, enteropathy, X-linked-like syndrome, and defective IL-10 expression from CD4 lymphocytes.
abstract: BACKGROUND
  Immune dysregulation, polyendocrinopathy, enteropathy, X-linked (IPEX) results in systemic autoimmunity from birth and can be caused by mutations in the transcription factor forkhead box P3 (FOXP3).
  
  
  OBJECTIVE
  To determine if Foxp3 is required for the generation of IL-10-expressing T regulatory cells.
  
  
  METHODS
  CD4 lymphocytes were isolated from patients with IPEX-like syndromes and activated with antibodies to CD3 and CD46 to generate IL-10-expressing T regulatory cells.
  
  
  RESULTS
  We describe a patient with clinical manifestations of IPEX that had a normal Foxp3 gene, but who had CD25 deficiency due to autosomal recessive mutations in this gene. This patient exhibited defective IL-10 expression from CD4 lymphocytes, whereas a Foxp3-deficient patient expressed normal levels of IL-10.
  
  
  CONCLUSIONS
  These data show that CD25 deficiency results in an IPEX-like syndrome and suggests that although Foxp3 is not required for normal IL-10 expression by human CD4 lymphocytes, CD25 expression is important.
  
  
  CONCLUSIONS
  Any patient with features of IPEX but with a normal Foxp3 gene should be screened for mutations in the IL-2 receptor subunit CD25.
authors.affiliation: Lewis-Sigler Institute for Integrative Genomics, Princeton University, Princeton, NJ, USA.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Caudy
authors.forename: Sreelatha T
authors.initials: ST
authors.lastname: Reddy
authors.forename: Talal
authors.initials: T
authors.lastname: Chatila
authors.forename: John P
authors.initials: JP
authors.lastname: Atkinson
authors.forename: James W
authors.initials: JW
authors.lastname: Verbsky
mesh_terms: D000483:Alleles; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002648:Child; D051858:Forkhead Transcription Factors / Q000235:genetics; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis*; D019409:Interleukin-15 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D053645:Interleukin-2 Receptor alpha Subunit / Q000172:deficiency* / Q000235:genetics; D007410:Intestinal Diseases / Q000235:genetics*; D008297:Male; D016884:Polyendocrinopathies, Autoimmune / Q000235:genetics*; D013577:Syndrome
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D019409:Interleukin-15; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D016753:Interleukin-10