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Epigenetic modification of FOXP3 in patients with chronic HIV infection.

ABSTRACT: OBJECTIVES: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.

SUBMITTER: Abdel-Hameed EA

PROVIDER: S-EPMC3871978 | biostudies-literature | 2014 Jan

REPOSITORIES: biostudies-literature

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Epigenetic modification of FOXP3 in patients with chronic HIV infection.

Abdel-Hameed Enass A EA Ji Hong H Sherman Kenneth E KE Shata Mohamed T M MT

Journal of acquired immune deficiency syndromes (1999) 20140101 1

<h4>Objectives</h4>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 comm ...[more]

PMID: 23846566

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Dataset Information

Epigenetic modification of FOXP3 in patients with chronic HIV infection.

Publications

Epigenetic modification of FOXP3 in patients with chronic HIV infection.

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