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Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation

Nature Medicine volume 24, pages 224–231 (2018)Cite this article

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Abstract

Myeloid-derived suppressor cells (MDSCs) are pathologically activated and relatively immature myeloid cells that have been implicated in the immunological regulation of many pathologic conditions1,2. Phenotypically and morphologically, MDSCs are similar to neutrophils (PMN-MDSCs) and monocytes (M-MDSCs). However, they have potent suppressive activity and distinct gene expression profiles and biochemical characteristics3. No or very few MDSCs are observed in steady-state physiological conditions. Therefore, until recently, accumulation of MDSCs was considered a consequence of pathological processes or pregnancy. Here, we report that MDSCs with a potent ability to suppress T cells are present during the first weeks of life in mice and humans. MDSC suppressive activity was triggered by lactoferrin and mediated by nitric oxide, PGE2, and S100A9 and S100A8 proteins. MDSCs from newborns had a transcriptome similar to that of tumor MDSCs, but with strong upregulation of an antimicrobial gene network, and had potent antibacterial activity. MDSCs played a critical role in control of experimental necrotizing enterocolitis (NEC) in newborn mice. MDSCs in infants with very low weight, who are prone to NEC, had lower MDSC levels and suppressive activity than did infants with normal weight. Thus, the transitory presence of MDSCs may be critical for regulation of inflammation in newborns.

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Figure 1: Expansion of MDSCs in NBM.
Figure 2: Lactoferrin is responsible for accumulation of MDSCs in NBM.
Figure 3: MDSCs in human infants.
Figure 4: Role of MDSCs in a necrotizing enterocolitis (NEC) experimental model.

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Acknowledgements

This work was supported by the Wistar Institute Animal and Bioinformatics core facilities as well as NIH grant CA165065 to D.I.G. and V.K. The work was also supported by the Recruitment Program for Foreign Experts (Thousand Talents Plan, WQ2014440O204), the Start-up Fund for High-level Talents of Sun Yat-sen University, and the Leading Talents of Guangdong Province Program (D.I.G.). This work was supported by the following grants to J.Z.: the Introduction of Innovative R&D Team Program of Guangdong Province (2009010058), the Guangdong Province Universities and Colleges Pearl River Scholar Funded Scheme (GDUPS, 2014), the National Natural Science Foundation of China (91542112; 81571520, 81771665, and 81742002), and the Provincial Talents Cultivated by the 'Thousand-Hundred-Ten' Program of Guangdong Province, 111 Project (B12003). We thank S. Grey-Owen (University of Toronto) and O.M. Conneely (Baylor College of Medicine) for providing LF-KO mice and T. Vogl and J. Roth (Institute of Immunology, Muenster) for providing S100A9-KO mice. We thank Y. Yu (Tianjin Medical University) for providing Cox-2-KO mice and H. Zhang (Sun Yat-sen University) for providing OT-1 transgenic mice.

Author information

Author notes

  1. Yu-Mei He, Xing Li and Michela Perego: These authors contributed equally to this work.

  2. Dmitry I Gabrilovich and Jie Zhou: These authors jointly directed this work.

Authors and Affiliations

  1. Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China

    Yu-Mei He, Xing Li, Yu-Feng Liu, Shu-Yu Fu, Dmitry I Gabrilovich & Jie Zhou

  2. Key Laboratory of Tropical Disease Control, Chinese Ministry of Education, Guangzhou, China

    Yu-Mei He, Xing Li, Dmitry I Gabrilovich & Jie Zhou

  3. Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

    Xing Li & Qing-Jian Ye

  4. Wistar Institute, Philadelphia, Pennsylvania, USA

    Michela Perego, Yulia Nefedova, Andrew V Kossenkov & Dmitry I Gabrilovich

  5. Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA

    Erik A Jensen

  6. Department of Environmental and Occupational Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Valerian Kagan

  7. Guangzhou Women and Children's Medical Center, Guangzhou, China

    Yan-Hong Zhou & Jie Zhou

  8. Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China

    Lai Wei

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Contributions

Conceptualization, D.I.G. and J.Z.; formal analysis, A.V.K.; investigation, Y.-M.H., X.L., M.P., Y.-F.L., S.-Y.F., Q.-J.Y., Y.-H.Z., and L.W.; resources, Y.N. and E.A.J.; writing original draft, D.I.G. and J.Z.; manuscript review and editing, D.I.G., J.Z., Y.N., and V.K.; supervision, D.I.G. and J.Z.; funding acquisition, D.I.G., J.Z., and V.K.

Corresponding authors

Correspondence to Dmitry I Gabrilovich or Jie Zhou.

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He, YM., Li, X., Perego, M. et al. Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation. Nat Med 24, 224–231 (2018). https://doi.org/10.1038/nm.4467

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