Unknown

Dataset Information

0

Histone deacetylase inhibition facilitates GM-CSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo.


ABSTRACT: Chromatin-modifying HDACi exhibit anti-inflammatory properties that reflect their ability to suppress DC function and enhance regulatory T cells. The influence of HDACi on MDSCs, an emerging regulatory leukocyte population that potently inhibits T cell proliferation, has not been examined. Exposure of GM-CSF-stimulated murine BM cells to HDACi led to a robust expansion of monocytic MDSC (CD11b(+)Ly6C(+)F4/80(int)CD115(+)), which suppressed allogeneic T cell proliferation in a NOS- and HO-1-dependent manner with similar potency to control MDSCs. The increased yield of MDSCs correlated with blocked differentiation of BM cells and an overall increase in HSPCs (Lin(-)Sca-1(+)c-Kit(+)). In vivo, TSA enhanced the mobilization of splenic HSPCs following GM-CSF administration and increased the number of CD11b(+)Gr1(+) cells in BM and spleen. Increased numbers of Gr1(+) cells, which suppressed T cell proliferation, were recovered from spleens of TSA-treated mice. Overall, HDACi enhance MDSC expansion in vitro and in vivo, suggesting that acetylation regulates myeloid cell differentiation. These findings establish a clinically applicable approach to augment this rare and potent suppressive immune cell population and support a novel mechanism underlying the anti-inflammatory action of HDACi.

SUBMITTER: Rosborough BR 

PROVIDER: S-EPMC4046249 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

altmetric image

Publications

Histone deacetylase inhibition facilitates GM-CSF-mediated expansion of myeloid-derived suppressor cells in vitro and in vivo.

Rosborough Brian R BR   Castellaneta Antonino A   Natarajan Sudha S   Thomson Angus W AW   Turnquist Heth R HR  

Journal of leukocyte biology 20111025 5


Chromatin-modifying HDACi exhibit anti-inflammatory properties that reflect their ability to suppress DC function and enhance regulatory T cells. The influence of HDACi on MDSCs, an emerging regulatory leukocyte population that potently inhibits T cell proliferation, has not been examined. Exposure of GM-CSF-stimulated murine BM cells to HDACi led to a robust expansion of monocytic MDSC (CD11b(+)Ly6C(+)F4/80(int)CD115(+)), which suppressed allogeneic T cell proliferation in a NOS- and HO-1-depen  ...[more]

Similar Datasets

| S-EPMC6399310 | biostudies-literature
| S-EPMC8523982 | biostudies-literature
| S-EPMC5192067 | biostudies-literature
| S-EPMC7078258 | biostudies-literature
| S-EPMC7765083 | biostudies-literature
| S-EPMC5093920 | biostudies-literature
| S-EPMC3218014 | biostudies-literature
2021-10-04 | PXD027049 | Pride
| S-EPMC5559065 | biostudies-literature
| S-EPMC5531556 | biostudies-literature