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

Paola Vacca, Claudia Cantoni, Massimo Vitale, Carola Prato, Francesca Canegallo, Daniela Fenoglio, Nicola Ragni, Lorenzo Moretta, Maria Cristina Mingari

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)11918-11923
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number26
DOIs
Publication statusPublished - Jun 29 2010

Keywords

  • Indoleamine 2,3-dioxygenase
  • Regulatory T cells
  • Tolerance in pregnancy
  • Transforming growth factor β

ASJC Scopus subject areas

  • General

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