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Amniotic membrane extract differentially regulates human peripheral blood T cell subsets, monocyte subpopulations and myeloid dendritic cells

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Abstract

The discovery of the immunoregulatory potential of human amniotic membrane (hAM) propelled several studies focusing on its application for the treatment of immunological disorders. However, there is little information regarding the effects of hAM on distinct activation and differentiation stages of immune cells. Here, we aim to investigate the effect of human amniotic membrane extract (hAME) on the pattern of cytokine production by T cells, monocytes and myeloid dendritic cells (mDCs). For this purpose, peripheral blood mononuclear cells (PBMCs) from eight healthy individuals were stimulated in vitro in the presence or absence of hAME. Mitogen-induced proliferation of PBMCs and cytokine production among the distinct T cell functional compartments, monocyte subpopulations and mDCs were evaluated. hAME displayed an anti-proliferative effect and decreased the frequency of T cells producing tumor necrosis factor (TNF)α, interferon (IFN)γ and interleukin (IL)-2, for all T cell functional compartments. The frequency of IL-17 and IL-9-producing T cells was also reduced. The inhibition of mRNA expression of granzyme B, perforin and NKG2D by CD8+ T cells and γδ T cells and the augment of FoxP3 and IL-10 in CD4+ T cells and IL-10 in regulatory T cells were also observed. Furthermore, hAME inhibited IFNγ-induced protein (IP)-10 expression by classical and non-classical monocytes, without hampering the production of TNFα and IL-6 by monocytes and mDCs. These results suggest that hAME exerts an anti-inflammatory effect on T cells, still at a different extent for distinct T cell functional compartments.

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Acknowledgments

Ana Catarina Mamede (SFRH/BD/73649/2010) and Maria João Carvalho (SFRH/SINTD/60068/2009) wish to thank the Fundação para a Ciência e a Tecnologia (FCT, Portugal) for the PhD grants. The authors would also like to thank the Obstetrics Service of the Centro Hospitalar e Universitário de Coimbra for the collection of human tissues used in this work.

Funding

Ana Catarina Mamede and Maria João Carvalho received PhD grants (SFRH/BD/73649/2010 and SFRH/SINTD/60068/2009, respectively) by Fundação para a Ciência e a Tecnologia (FCT), Portugal. This study was funded by Infarmed (Health Research Fund 2015, FIS-2015-01), Portugal.

Author information

Author notes

  1. Paula Laranjeira and Marta Duque contributed equally to this work.

Authors and Affiliations

  1. Blood and Transplantation Center of Coimbra, Portuguese Institute of the Blood and Transplantation, Quinta da Vinha Moura, São Martinho do Bispo, 3041-861, Coimbra, Portugal

    Paula Laranjeira, Marta Duque, Maria J. Inácio, Isabel Silva, Susana Pedreiro, António Martinho, Hélder Trindade & Artur Paiva

  2. Flow Cytometry Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, Ed. S. Jerónimo, Piso 3, 3000-075, Coimbra, Portugal

    Paula Laranjeira, Isabel Silva, Susana Pedreiro & Artur Paiva

  3. Department of Chemistry, University of Aveiro, 3810-193, Aveiro, Portugal

    Marta Duque, Pedro Domingues & Rosário Domingues

  4. University of Veterinary Medicine and Pharmacy in Košice, Komenského 73, 041 81, Košice, Slovakia

    Martin Vojtek

  5. Faculty of Pharmacy, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Martin Vojtek

  6. Biophysics Institute, Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Ana C. Mamede, Mafalda Laranjo, Maria J. Carvalho, Ana M. Abrantes & Maria F. Botelho

  7. Centre of Investigation on Environment, Genetics and Oncobiology (CIMAGO), Faculty of Medicine, University of Coimbra, Apartado 9015, 3001-301, Coimbra, Portugal

    Ana C. Mamede, Mafalda Laranjo, Maria J. Carvalho, Ana M. Abrantes & Maria F. Botelho

  8. CNC-IBILI, Faculty of Medicine, University of Coimbra, Pólo das Ciências da Saúde, Azinhaga de Santa Comba, 3000-548, Coimbra, Portugal

    Ana C. Mamede, Mafalda Laranjo, Maria J. Carvalho, Ana M. Abrantes & Maria F. Botelho

  9. CICS-UBI, Health Sciences Research Center, University of Beira Interior, Av. Infante D. Henrique, 6201-506, Covilhã, Portugal

    Ana C. Mamede & Cláudio J. Maia

  10. Obstetrics Unit, Hospitais da Universidade de Coimbra, Centro Hospitalar e Universitário de Coimbra, Praceta Prof. Mota Pinto, 3000-075, Coimbra, Portugal

    Maria J. Carvalho & Paulo Moura

Authors
  1. Paula Laranjeira
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  2. Marta Duque
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  4. Maria J. Inácio
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  5. Isabel Silva
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Correspondence to Artur Paiva.

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The authors declare that they have no conflict of interest.

Ethical approval

The study was approved by the Ethical Committee of the Centro Hospitalar e Universitário de Coimbra (CHUC-70-12, Coimbra, Portugal). All procedures performed in the studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments.

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Informed consent was obtained from all individual participants included in the study.

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Laranjeira, P., Duque, M., Vojtek, M. et al. Amniotic membrane extract differentially regulates human peripheral blood T cell subsets, monocyte subpopulations and myeloid dendritic cells. Cell Tissue Res 373, 459–476 (2018). https://doi.org/10.1007/s00441-018-2822-1

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