Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells
Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2013-01-01
|
| Series: | Clinical and Developmental Immunology |
| Online Access: | http://dx.doi.org/10.1155/2013/679804 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832553514567467008 |
|---|---|
| author | Cristian Doñas Macarena Fritz Valeria Manríquez Gabriela Tejón María Rosa Bono Alejandra Loyola Mario Rosemblatt |
| author_facet | Cristian Doñas Macarena Fritz Valeria Manríquez Gabriela Tejón María Rosa Bono Alejandra Loyola Mario Rosemblatt |
| author_sort | Cristian Doñas |
| collection | DOAJ |
| description | Regulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells. |
| format | Article |
| id | doaj-art-027f8d9919c647dea76e3e7eea3e2ebd |
| institution | Kabale University |
| issn | 1740-2522 1740-2530 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Developmental Immunology |
| spelling | doaj-art-027f8d9919c647dea76e3e7eea3e2ebd2025-02-03T05:53:48ZengWileyClinical and Developmental Immunology1740-25221740-25302013-01-01201310.1155/2013/679804679804Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T CellsCristian Doñas0Macarena Fritz1Valeria Manríquez2Gabriela Tejón3María Rosa Bono4Alejandra Loyola5Mario Rosemblatt6Departamento de Ciencias Biológicas, Universidad Andrés Bello, República 275, Santiago, ChileDepartamento de Ciencias Biológicas, Universidad Andrés Bello, República 275, Santiago, ChileLaboratorio de Inmunología, Departamento de Biología, Facultad de Ciencias, Las Palmeras 3425, Ñuñoa, Universidad de Chile, Santiago, ChileLaboratorio de Inmunología, Departamento de Biología, Facultad de Ciencias, Las Palmeras 3425, Ñuñoa, Universidad de Chile, Santiago, ChileLaboratorio de Inmunología, Departamento de Biología, Facultad de Ciencias, Las Palmeras 3425, Ñuñoa, Universidad de Chile, Santiago, ChileFundación Ciencia & Vida, Avenida Zañartu 1482, Ñuñoa, Santiago, ChileDepartamento de Ciencias Biológicas, Universidad Andrés Bello, República 275, Santiago, ChileRegulatory T cells are a specific subset of lymphocytes that suppress immune responses and play a crucial role in the maintenance of self-tolerance. They can be generated in the thymus as well as in the periphery through differentiation of naïve CD4+ T cells. The forkhead box P3 transcription factor (Foxp3) is a crucial molecule regulating the generation and function of Tregs. Here we show that the foxp3 gene promoter becomes hyperacetylated in in vitro differentiated Tregs compared to naïve CD4+ T cells. We also show that the histone deacetylase inhibitor TSA stimulated the in vitro differentiation of naïve CD4+ T cells into Tregs and that this induction was accompanied by a global increase in histone H3 acetylation. Importantly, we also demonstrated that Tregs generated in the presence of TSA have phenotypical and functional differences from the Tregs generated in the absence of TSA. Thus, TSA-generated Tregs showed increased suppressive activities, which could potentially be explained by a mechanism involving the ectonucleotidases CD39 and CD73. Our data show that TSA could potentially be used to enhance the differentiation and suppressive function of CD4+Foxp3+ Treg cells.http://dx.doi.org/10.1155/2013/679804 |
| spellingShingle | Cristian Doñas Macarena Fritz Valeria Manríquez Gabriela Tejón María Rosa Bono Alejandra Loyola Mario Rosemblatt Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells Clinical and Developmental Immunology |
| title | Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells |
| title_full | Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells |
| title_fullStr | Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells |
| title_full_unstemmed | Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells |
| title_short | Trichostatin A Promotes the Generation and Suppressive Functions of Regulatory T Cells |
| title_sort | trichostatin a promotes the generation and suppressive functions of regulatory t cells |
| url | http://dx.doi.org/10.1155/2013/679804 |
| work_keys_str_mv | AT cristiandonas trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells AT macarenafritz trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells AT valeriamanriquez trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells AT gabrielatejon trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells AT mariarosabono trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells AT alejandraloyola trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells AT mariorosemblatt trichostatinapromotesthegenerationandsuppressivefunctionsofregulatorytcells |