Crosstalk between decidual NK and CD14⁺ myelomonocytic cells results in induction of Tregs and immunosuppression

Regulatory T cells (Tregs) are thought to play a major role in pregnancy by inhibiting the maternal immune system and preventing fetal rejection. In decidual tissues, NK cells (dNK) reside in close contact with particular myelomonocytic CD14⁺ (dCD14⁺) cells. Here we show that the interaction between...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2010-06, Vol.107 (26), p.11918-11923
Main Authors: Vacca, Paola, Cantoni, Claudia, Vitale, Massimo, Prato, Carola, Canegallo, Francesca, Fenoglio, Daniela, Ragni, Nicola, Moretta, Lorenzo, Mingari, Maria Cristina
Format: Article
Language:English
Subjects:
Antigens, CD - metabolism
Base Sequence
Biological Sciences
Blood
Cell Communication - immunology
Cell growth
Cells
Coculture techniques
Crosstalk
CTLA-4 Antigen
Cultured cells
Decidua - cytology
Decidua - immunology
Delta cells
Dendritic cells
DNA Primers - genetics
Female
Gene expression
Humans
Immune system
Immune Tolerance - immunology
Immunology
In Vitro Techniques
Indoleamine-Pyrrole 2,3,-Dioxygenase - genetics
Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism
Interferon-gamma - metabolism
Killer Cells, Natural - immunology
Killer Cells, Natural - metabolism
Kynurenine - metabolism
Lipopolysaccharide Receptors - metabolism
Myeloid Cells - immunology
Myeloid Cells - metabolism
Natural killer cells
Pregnancy
Pregnancy - immunology
Proteins
Receptors
T-Lymphocytes, Regulatory - immunology
T-Lymphocytes, Regulatory - metabolism
Tissues
Transforming Growth Factor beta - metabolism
Tryptophan - metabolism
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Summary:Regulatory T cells (Tregs) are thought to play a major role in pregnancy by inhibiting the maternal immune system and preventing fetal rejection. In decidual tissues, NK cells (dNK) reside in close contact with particular myelomonocytic CD14⁺ (dCD14⁺) cells. Here we show that the interaction between dNK and dCD14⁺ cells results in induction of Tregs. The interaction is mediated by soluble factors as shown by transwell experiments, and the prominent role of IFN-γ is revealed by the effect of a neutralizing monoclonal antibody. Following interaction with dNK cells, dCD14⁺ cells express indoleamine 2,3-dioxygenase (IDO), which, in turn, induces Tregs. Notably, unlike peripheral blood NK (pNK) cells, dNK cells are resistant to inhibition by the IDO metabolite L-kynurenine. "Conditioned" dCD14⁺ cells also may induce Tregs through transforming growth factor-β (TGF-β) production or CTLA-4-mediated interactions, as indicated by the effect of specific neutralizing Abs. Remarkably, only the interaction between dNK and dCD14⁺ cells results in Treg induction, whereas other coculture combinations involving either NK or CD14⁺ cells isolated from peripheral blood are ineffective. Our study provides interesting clues to understanding how the crosstalk between decidual NK and CD14⁺ cells may initiate a process that leads to Treg induction and immunosuppression. Along this line, it is conceivable that an impaired function of these cells may result in pregnancy failure.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1001749107