title: Epigenetic modification of FOXP3 in patients with chronic HIV infection.
abstract: OBJECTIVE
  HIV-1 modulates host cell epigenetic machinery to control its own replication and induce immune suppression. HIV-1 infection leads to activation of T regulatory cell (T(reg)), but the mechanism underlying this immune modulation is unclear. T(reg) plays a prominent role in gut-mucosal immune tolerance by restraining excessive effector T-cell responses, a mechanism that is known to be disturbed in chronic HIV-1 infection. DNA methylation plays a major role in T(reg) lineage commitment and immune homeostasis, which may be regulated by HIV. To investigate the mechanisms of aberrant methylation of the T(reg) marker FOXP3 in HIV-1 infection, we evaluated the expression pattern of methylation-related enzymes and its correlation to FOXP3 methylation.
  
  
  METHODS
  FOXP3 promoter methylation in the colon mucosa and peripheral blood from HIV-infected patients and control subjects was measured using Pyrosequencing. Gene expression pattern of DNA methylation enzymes in the colon mucosa was investigated by Microarray and quantitative reverse transcriptase-polymerase chain reaction analysis in the same subjects.
  
  
  RESULTS
  FOXP3 promoter was significantly (P ≤ 0.0001) demethylated in HIV-infected patients compared with control subjects in both tissues. Expression of DNA methyltransferase 1 (DNAMT1), DNA methyltransferase 1-associated protein 1(DMAP1), methyltransferase-like 7B (METTL7B), and methyltransferase-like 10 (METTL10) were significantly down regulated in HIV-infected patients compared with controls and had a significant positive correlation to FOXP3 promoter methylation.
  
  
  CONCLUSIONS
  We present evidence suggesting that altered methylation pattern of FOXP3 and accordingly higher T(reg) frequency in gut mucosa of HIV-infected patients may be because of aberrant methylation processing in HIV.
authors.affiliation: *Department of Internal Medicine, Division of Digestive Diseases, University of Cincinnati Medical Center, Cincinnati, OH; and †Division of Asthma Research, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH.
authors.forename: Enass A
authors.initials: EA
authors.lastname: Abdel-Hameed
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Sherman
authors.forename: Mohamed T M
authors.initials: MT
authors.lastname: Shata
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism; D019175:DNA Methylation / Q000502:physiology*; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism / Q000502:physiology*; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology*; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D059467:Transcriptome / Q000502:physiology; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors