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The role of natural killer cells in the uterine microenvironment during pregnancy

Cellular & Molecular Immunology volume 15, pages 941–943 (2018)Cite this article

Pregnancy is a choreographed physiological phenomenon that involves maternal-fetal cross-talk. Elucidating the cellular and molecular mechanisms involved in this communication will allow us to develop therapies for gestational complications. Little is known about the role of natural killer (NK) cells in the uterine microenvironment. In a recent study, Fu et al. (2017) used state-of-art technologies and showed that NK cells stimulate fetal growth via growth-promoting factors.

Strikingly, transplantation of uterine NK cells from normal mice reversed the negative pregnancy outcome in NK cell-deficient transgenic mice, as well as in aged mice. This new knowledge provides insight into the role of NK cells in the uterine microenvironment during pregnancy.

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References

  1. Bazer, F. W. et al. Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Mol. Hum. Reprod. 16, 135–152 (2010).

    Article  CAS  Google Scholar 

  2. Birbrair, A. Stem cell microenvironments and beyond. Adv. Exp. Med. Biol. 1041, 1–3 (2017).

    Article  CAS  Google Scholar 

  3. Jabrane-Ferrat, N. & Siewiera, J. The up side of decidual natural killer cells: new developments in immunology of pregnancy. Immunology 141, 490–497 (2014).

    Article  CAS  Google Scholar 

  4. Padro Dietz, C. & Luong, A. Innate lymphoid cells: the innate counterpart to T helper cells. Adv. Otorhinolaryngol. 79, 58–68 (2016).

    PubMed  Google Scholar 

  5. Fu, B. et al. Natural killer cells promote fetal development through the secretion of growth-promoting factors. Immunity 47, 1100–1113 (2017). e1106-1113.e6.

    Article  CAS  Google Scholar 

  6. Teles, A. et al. Control of uterine microenvironment by foxp3(+) cells facilitates embryo implantation. Front. Immunol. 4, 158 (2013).

    Article  Google Scholar 

  7. Mizugishi, K. et al. Sphingolipid pathway regulates innate immune responses at the fetomaternal interface during pregnancy. J. Biol. Chem. 290, 2053–2068 (2015).

    Article  CAS  Google Scholar 

  8. Birbrair, A. et al. Pericytes at the intersection between tissue regeneration and pathology. Clin. Sci. 128, 81–93 (2015).

    Article  CAS  Google Scholar 

  9. Dias Moura Prazeres, P. H. et al. Pericytes are heterogeneous in their origin within the same tissue. Dev. Biol. 427, 6–11 (2017).

    Article  Google Scholar 

  10. Azevedo, P. O. et al. Pericytes modulate myelination in the central nervous system. J. Cell. Physiol. https://doi.org/10.1002/jcp.26348 (2017).

    Article  CAS  Google Scholar 

  11. Paiva, A. E. et al. Endothelial cells as precursors for osteoblasts in the metastatic prostate cancer bone. Neoplasia 19, 928–931 (2017).

    Article  CAS  Google Scholar 

  12. Costa, M. A. et al. Pericytes constrict blood vessels after myocardial ischemia. J. Mol. Cell Cardiol. 116, 1–4 (2018).

    Article  CAS  Google Scholar 

  13. Vacca, P., Moretta, L., Moretta, A. & Mingari, M. C. Origin, phenotype and function of human natural killer cells in pregnancy. Trends Immunol. 32, 517–523 (2011).

    Article  CAS  Google Scholar 

  14. Andreotti, J. P., Lousado, L., Magno, L. A. V. & Birbrair, A. Hypothalamic neurons take center stage in the neural stem cell niche. Cell Stem Cell 21, 293–294 (2017).

    Article  CAS  Google Scholar 

  15. Guerra, D. A. P. et al. Adipocytes role in the bone marrow niche. Cytom. A 93, 167–171 (2017).

    Article  Google Scholar 

  16. Motomura, Y. et al. The transcription factor E4BP4 regulates the production of IL-10 and IL-13 in CD4+ T cells. Nat. Immunol. 12, 450–459 (2011).

    Article  CAS  Google Scholar 

  17. MacGillavry, H. D. et al. NFIL3 and cAMP response element-binding protein form a transcriptional feedforward loop that controls neuronal regeneration-associated gene expression. J. Neurosci. 29, 15542–15550 (2009).

    Article  CAS  Google Scholar 

  18. Jewett, A., Man, Y. G. & Tseng, H. C. Dual functions of natural killer cells in selection and differentiation of stem cells; role in regulation of inflammation and regeneration of tissues. J. Cancer 4, 12–24 (2013).

    Article  CAS  Google Scholar 

  19. Zhang, J. et al. Human dNK cell function is differentially regulated by extrinsic cellular engagement and intrinsic activating receptors in first and second trimester pregnancy. Cell Mol. Immunol. 14, 203–213 (2017).

    Article  CAS  Google Scholar 

  20. Sena, I. F. G. et al. Glioblastoma-activated pericytes support tumor growth via immunosuppression. Cancer Med. https://doi.org/10.1002/cam4.1375 (2018).

    Article  Google Scholar 

Download references

Acknowledgements

A.B. is supported by a grant from Instituto Serrapilheira/Serra-1708-15285, a grant from Pró-reitoria de Pesquisa/Universidade Federal de Minas Gerais (PRPq/UFMG) (Edital 05/2016), a grant from FAPEMIG [Rede Mineira de Engenharia de Tecidos e Terapia Celular (REMETTEC, RED-00570-16)], and a grant from FAPEMIG [Rede De Pesquisa Em Doenças Infecciosas Humanas E Animais Do Estado De Minas Gerais (RED-00313-16)]. A.M. is supported by the National Institute of Health (1R01CA179072-01A1) and by the American Cancer Society Mentored Research Scholar grant (124443-MRSG-13-121-01-CDD).

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Authors and Affiliations

  1. Department of Pathology, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil

    Julia P. Andreotti, Ana E. Paiva, Pedro H. D. M. Prazeres, Daniel A. P. Guerra, Walison N. Silva & Alexander Birbrair

  2. Department of Biotechnology and Bioprocess Engineering, Federal University of Parana, Curitiba, PR, Brazil

    Rogerio S. Vaz

  3. Department of Radiology, Columbia University Medical Center, New York, NY, USA

    Akiva Mintz & Alexander Birbrair

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  1. Julia P. Andreotti
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Correspondence to Alexander Birbrair.

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Andreotti, J.P., Paiva, A.E., Prazeres, P.H.D.M. et al. The role of natural killer cells in the uterine microenvironment during pregnancy. Cell Mol Immunol 15, 941–943 (2018). https://doi.org/10.1038/s41423-018-0023-1

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