PD-1 is expressed by and regulates human group 3 innate lymphoid cells in human decidua

Paola Vacca, Silvia Pesce, Marco Greppi, Ezio Fulcheri, Enrico Munari, Daniel Olive, Maria Cristina Mingari, Alessandro Moretta, Lorenzo Moretta, Emanuela Marcenaro

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Group 3 innate lymphoid cells (ILC3) have been detected in both murine and human decidual tissues where they are thought to play a relevant role in the induction and maintenance of pregnancy. However, limited information exists on the molecular mechanisms that regulate these cells, including immune checkpoints. Here, we show that ILC3 express the inhibitory checkpoints programmed cell death (PD-1) and T cell immunoglobulin and mucin domain containing protein 3 (TIM-3) during the first trimester of pregnancy and that these receptors could regulate production of cytokines, including IL-22, IL-8, and TNF-α, induced by IL-23. We also show that the intermediate extravillous trophoblast (iEVT) expresses high levels of the PD-1-ligand PD-L1, suggesting that PD-1/PD-L1 interaction may regulate ILC3 function at the feto-maternal interface. Our present data provide the first evidence that human decidual ILC3 express a functional PD-1. It is possible that an altered expression or function of PD-1 may break the immune-tolerance resulting in pregnancy failure.

Original languageEnglish
Pages (from-to)624-631
Number of pages8
JournalMucosal Immunology
Issue number3
Publication statusPublished - May 2019


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