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Crucial role of histone deacetylase SIRT1 in myeloid-derived suppressor cell-mediated reprogramming of CD4+ T-cell differentiation

Cellular & Molecular Immunology volume 17, pages 785–787 (2020)Cite this article

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Myeloid-derived suppressor cells (MDSCs) are heterogeneous, immature myeloid cells that inhibit the immune responses of T cells.1,2,3,4,5 MDSCs play a crucial role in infection,6,7 transplantation,8,9 autoimmune diseases10,11, and tumors12,13 by driving the differentiation of specific T-cell subsets, but the precise regulatory mechanism is still unclear. Recently, our results showed that SIRT1, a histone deacetylase, suppresses the functions of proinflammatory MDSCs and promotes tumor growth.14 However, it remains unclear whether SIRT1 regulates the MDSC-induced differentiation of T cells. Here, we identified the regulatory effects of SIRT1 in CD11b+Gr1+ MDSCs on T-cell differentiation.

How does SIRT1 in MDSCs direct T cell differentiation? As previously reported,14,15 SIRT1 deletion promotes the costimulatory molecule expression and proinflammatory cytokine secretion of MDSCs and inhibits anti-inflammatory cytokine secretion (Fig. 1f). The cytokine environment is an important determinant of T cell differentiation.16,17,18,19,20 Therefore, we observed the effect of the secretion of different cytokines on the differentiation of T cell subsets. When T cells were cocultured with MDSCs in the presence of OVA, blocking IL-12 with a neutralizing antibody and adding IL-10 could not restore the differentiation of T cells (data not shown). However, interestingly, blocking TNFα with an antibody and adding TGFβ1 significantly reversed the TH1 and iTreg differentiation induced by SIRT1 deletion (Fig. 1g), suggesting that SIRT1 deficiency might affect the reciprocal differentiation of T cells by promoting TNFα secretion and inhibiting TGFβ1.

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References

  1. Medzhitov, R. et al. Highlights of 10 years of immunology in nature reviews immunology. Nat. Rev. Immunol. 11, 693–702 (2011).

    Article  CAS  Google Scholar 

  2. Veglia, F., Perego, M. & Gabrilovich, D. Myeloid-derived suppressor cells coming of age. Nat. Immunol. 19, 108–119 (2018).

    Article  CAS  Google Scholar 

  3. Kumar, V., Patel, S., Tcyganov, E. & Gabrilovich, D. I. The nature of myeloid-derived suppressor cells in the tumor microenvironment. Trends Immunol. 37, 208–220 (2016).

    Article  CAS  Google Scholar 

  4. Lu, Z. et al. Epigenetic therapy inhibits metastases by disrupting premetastatic niches. Nature https://doi.org/10.1038/s41586-020-2054-x (2020).

  5. Tsiganov, E. N. et al. Gr-1dimCD11b+ immature myeloid-derived suppressor cells but not neutrophils are markers of lethal tuberculosis infection in mice. J. Immunol. 192, 4718–4727 (2014).

    Article  CAS  Google Scholar 

  6. Weber, C. Hepatitis: myeloid-derived suppressor cells in HBV infection. Nat. Rev. Gastroenterol. Hepatol. 12, 370 (2015).

    Article  Google Scholar 

  7. Yang, F. et al. Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection. PLoS Pathog. 15, e1007690 (2019).

    Article  CAS  Google Scholar 

  8. Wang, X. et al. The calcineurin-NFAT axis controls allograft immunity in myeloid-derived suppressor cells through reprogramming T cell differentiation. Mol. Cell. Biol. 35, 598–609 (2015).

    Article  Google Scholar 

  9. Liao, J. et al. Dexamethasone potentiates myeloid-derived suppressor cell function in prolonging allograft survival through nitric oxide. J. Leukoc. Biol. 96, 675–684 (2014).

    Article  Google Scholar 

  10. Ji, J. et al. MDSCs: friend or foe in systemic lupus erythematosus. Cell. Mol. Immunol. 16, 937–939 (2019).

    Article  CAS  Google Scholar 

  11. Lu, Y. et al. Glucocorticoid receptor promotes the function of myeloid-derived suppressor cells by suppressing HIF1alpha-dependent glycolysis. Cell. Mol. Immunol. 15, 618–629 (2018).

    Article  CAS  Google Scholar 

  12. Nagaraj, S. et al. Antigen-specific CD4(+) T cells regulate function of myeloid-derived suppressor cells in cancer via retrograde MHC class II signaling. Cancer Res. 72, 928–938 (2012).

    Article  CAS  Google Scholar 

  13. Deng, J. et al. Hypoxia-induced VISTA promotes the suppressive function of myeloid-derived suppressor cells in the tumor microenvironment. Cancer Immunol. Res. 7, 1079–1090 (2019).

    Article  Google Scholar 

  14. Liu, G. et al. SIRT1 limits the function and fate of myeloid-derived suppressor cells in tumors by orchestrating HIF-1alpha-dependent glycolysis. Cancer Res. 74, 727–737 (2014).

    Article  CAS  Google Scholar 

  15. Chalkiadaki, A. & Guarente, L. Sirtuins mediate mammalian metabolic responses to nutrient availability. Nat. Rev. Endocrinol. 8, 287–296 (2012).

    Article  CAS  Google Scholar 

  16. Zhu, J., Yamane, H. & Paul, W. E. Differentiation of effector CD4 T cell populations (*). Annu. Rev. Immunol. 28, 445–489 (2010).

    Article  CAS  Google Scholar 

  17. Li, C. et al. Dendritic cell MST1 inhibits Th17 differentiation. Nat. Commun. 8, 14275 (2017).

    Article  CAS  Google Scholar 

  18. Wang, Y. et al. Histone deacetylase SIRT1 negatively regulates the differentiation of interleukin-9-producing CD4(+) T cells. Immunity 44, 1337–1349 (2016).

    Article  CAS  Google Scholar 

  19. Liu, G., Yang, K., Burns, S., Shrestha, S. & Chi, H. The S1P(1)-mTOR axis directs the reciprocal differentiation of T(H)1 and T(reg) cells. Nat. Immunol. 11, 1047–1056 (2010).

    Article  CAS  Google Scholar 

  20. Liu, G. et al. The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTOR. Nat. Immunol. 10, 769–777 (2009).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors’ research is supported by grants from the National Natural Science Foundation for Key Programs of China (31730024, G.L.) and the National Natural Science Foundation for General Programs of China (31671524, G.L.).

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  1. These authors contributed equally: Lin Dong, Yujing Bi, Anna Jia, Qing Yu

Authors and Affiliations

  1. Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, Institute of Cell Biology, College of Life Sciences, Beijing Normal University, 100875, Beijing, China

    Lin Dong, Anna Jia, Qing Yu, Yuexin Wang, Yufei Wang, Qiuli Yang, Yejin Cao, Ying He, Ruichen Liu, Yan Li & Guangwei Liu

  2. State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 100071, Beijing, China

    Yujing Bi

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Contributions

L.D., Y.B., A.J., and Q.Y. designed and conducted the experiment with cells and mice and analyzed the data; Y.X.W., Y.F.W., Q.L.Y., Y.C., Y.H., R.L., and Y.L. participated in discussions; L.D. and Y.B. contributed to writing the paper; and G.L. developed the concept, designed and conducted the experiments, analyzed data, wrote the paper, and provided overall direction.

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Correspondence to Guangwei Liu.

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Dong, L., Bi, Y., Jia, A. et al. Crucial role of histone deacetylase SIRT1 in myeloid-derived suppressor cell-mediated reprogramming of CD4+ T-cell differentiation. Cell Mol Immunol 17, 785–787 (2020). https://doi.org/10.1038/s41423-020-0419-6

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