Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways.
Forkhead box (Fox)/winged-helix transcription factors regulate multiple aspects of immune responsiveness and Foxp3 is recognized as an essential functional marker of regulatory T cells. Herein we describe downstream signaling pathways targeted by Foxp3 that may negatively impact retroviral pathogene...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2006-04-01
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| Series: | PLoS Pathogens |
| Online Access: | http://europepmc.org/articles/PMC1447668?pdf=render |
| _version_ | 1830484347859238912 |
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| author | Christian Grant Unsong Oh Kazunori Fugo Norihiro Takenouchi Caitlin Griffith Karen Yao Timothy E Newhook Lee Ratner Steven Jacobson |
| author_facet | Christian Grant Unsong Oh Kazunori Fugo Norihiro Takenouchi Caitlin Griffith Karen Yao Timothy E Newhook Lee Ratner Steven Jacobson |
| author_sort | Christian Grant |
| collection | DOAJ |
| description | Forkhead box (Fox)/winged-helix transcription factors regulate multiple aspects of immune responsiveness and Foxp3 is recognized as an essential functional marker of regulatory T cells. Herein we describe downstream signaling pathways targeted by Foxp3 that may negatively impact retroviral pathogenesis. Overexpression of Foxp3 in HEK 293T and purified CD4+ T cells resulted in a dose-dependent and time-dependent decrease in basal levels of nuclear factor-kappaB (NF-kappaB) activation. Deletion of the carboxyl-terminal forkhead (FKH) domain, critical for nuclear localization and DNA-binding activity, abrogated the ability of Foxp3 to suppress NF-kappaB activity in HEK 293T cells, but not in Jurkat or primary human CD4+ T cells. We further demonstrate that Foxp3 suppressed the transcription of two human retroviral promoters (HIV-1 and human T cell lymphotropic virus type I [HTLV-I]) utilizing NF-kappaB-dependent and NF-kappaB-independent mechanisms. Examination of the latter identified the cAMP-responsive element binding protein (CREB) pathway as a target of Foxp3. Finally, comparison of the percent Foxp3+CD4+CD25+ T cells to the HTLV-I proviral load in HTLV-I-infected asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggested that high Foxp3 expression is associated with low proviral load and absence of disease. These results suggest an expanded role for Foxp3 in regulating NF-kappaB- and CREB-dependent cellular and viral gene expression. |
| first_indexed | 2024-12-21T18:06:33Z |
| format | Article |
| id | doaj.art-6d9c31bcd5c546b8a65a93ad9df07ccc |
| institution | Directory Open Access Journal |
| issn | 1553-7366 1553-7374 |
| language | English |
| last_indexed | 2024-12-21T18:06:33Z |
| publishDate | 2006-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Pathogens |
| spelling | doaj.art-6d9c31bcd5c546b8a65a93ad9df07ccc2022-12-21T18:54:55ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742006-04-0124e3310.1371/journal.ppat.0020033Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways.Christian GrantUnsong OhKazunori FugoNorihiro TakenouchiCaitlin GriffithKaren YaoTimothy E NewhookLee RatnerSteven JacobsonForkhead box (Fox)/winged-helix transcription factors regulate multiple aspects of immune responsiveness and Foxp3 is recognized as an essential functional marker of regulatory T cells. Herein we describe downstream signaling pathways targeted by Foxp3 that may negatively impact retroviral pathogenesis. Overexpression of Foxp3 in HEK 293T and purified CD4+ T cells resulted in a dose-dependent and time-dependent decrease in basal levels of nuclear factor-kappaB (NF-kappaB) activation. Deletion of the carboxyl-terminal forkhead (FKH) domain, critical for nuclear localization and DNA-binding activity, abrogated the ability of Foxp3 to suppress NF-kappaB activity in HEK 293T cells, but not in Jurkat or primary human CD4+ T cells. We further demonstrate that Foxp3 suppressed the transcription of two human retroviral promoters (HIV-1 and human T cell lymphotropic virus type I [HTLV-I]) utilizing NF-kappaB-dependent and NF-kappaB-independent mechanisms. Examination of the latter identified the cAMP-responsive element binding protein (CREB) pathway as a target of Foxp3. Finally, comparison of the percent Foxp3+CD4+CD25+ T cells to the HTLV-I proviral load in HTLV-I-infected asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggested that high Foxp3 expression is associated with low proviral load and absence of disease. These results suggest an expanded role for Foxp3 in regulating NF-kappaB- and CREB-dependent cellular and viral gene expression.http://europepmc.org/articles/PMC1447668?pdf=render |
| spellingShingle | Christian Grant Unsong Oh Kazunori Fugo Norihiro Takenouchi Caitlin Griffith Karen Yao Timothy E Newhook Lee Ratner Steven Jacobson Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. PLoS Pathogens |
| title | Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. |
| title_full | Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. |
| title_fullStr | Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. |
| title_full_unstemmed | Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. |
| title_short | Foxp3 represses retroviral transcription by targeting both NF-kappaB and CREB pathways. |
| title_sort | foxp3 represses retroviral transcription by targeting both nf kappab and creb pathways |
| url | http://europepmc.org/articles/PMC1447668?pdf=render |
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