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| Content Provider | PubMed Central |
|---|---|
| Author | José, Medina-echeverz Haile, Lydia A. Zhao, Fei Jaba, Gamrekelashvili Ma, Chi Métais, Jean-yves Dunbar, Cynthia E. Kapoor, Veena Manns, Michael P. Korangy, Firouzeh Greten, Tim F. |
| Abstract | Myeloid derived suppressor cells (MDSCs) play a critical role in suppression of immune responses in cancer and inflammation. Here, we describe how regulation of Bcl2a1 by cytokines controls the suppressor function of CD11b+Gr-1high granulocytic MDSCs. Co-culture of CD11b+Gr-1high granulocytic MDSCs with antigen-stimulated T cells and simultaneous blockade of IFN-γ by the use of anti-IFN-γ blocking antibody, IFN-γ−/− effector T cells, IFN-γR−/− MDSCs or STAT1−/− MDSCs led to up-regulation of Bcl2a1 in CD11b+Gr-1high cells, improved survival and enhanced their suppressor function. Molecular studies revealed that GM-CSF released by antigen-stimulated CD8+ T cells induced Bcl2a1 up-regulation, which was repressed in the presence of IFN-γ by a direct interaction of phosphorylated STAT-1 with the Bcl2a1 promotor. Bcl2a1 overexpressing granulocytic MDSCs demonstrated prolonged survival and enhanced suppressor function in vitro. Our data suggest that IFN-γ/ STAT1-dependent regulation of Bcl2a1 regulates survival and thereby suppressor function of granulocytic MDSCs. |
| Related Links | http://dx.doi.org/10.1002/eji.201444497 |
| Ending Page | 2467 |
| Page Count | 11 |
| Starting Page | 2457 |
| File Format | |
| ISSN | 00142980 |
| e-ISSN | 15214141 |
| Journal | European journal of immunology |
| Issue Number | 8 |
| Volume Number | 44 |
| Language | English |
| Publisher Date | 2014-08-01 |
| Access Restriction | Open |
| Subject Keyword | Immunology Immunology and Allergy Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
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