Adam Jelinski, MSc1, Shuang-Yin Wang, PhD1, Moriya Gamliel, PhD2, Naama Elefant, MD, PhD1, Debra Goldman-Wohl, PhD2, Ronit Gilad, MD2, Yishai Sompolinsky, MD, MPH2, Ofer Mandelboim, PhD2, Simcha Yagel, MD2, Ido Amit, PhD1.
1Weizmann Institute of Science, Rehovot,, 2Hadassah-Hebrew University Medical Center, Jerusalem, Israel
Introduction: A dedicated decidual immunomodulatory mechanism evolved to allow healthy embryo development alongside maternal immune protection and homeostasis. Decidual NK (dNK) cells comprise the overwhelming majority of immune cells in the decidua. They play a pivotal role with beneficial properties in development of the maternal fetal interface. Our objective is to characterize the decidual immune cell profile using novel technology with a focus on dNK cells.
Methods: Massively parallel single cell RNA-seq was used to characterize more than 30,000 immune cells from 20 first trimester (Figure 1) and 2 early second trimester deciduas.
Results: Unbiased analysis revealed immune cell populations including previously undescribed subpopulations of dNK and ILC1 (innate lymphoid) cells. Some dNK show high abundance of cytotoxic agents such as GZMA, GZMB and GNLY (“cytotoxic dNK”). In another dNK population we identify a transcriptional program more skewed towards secretion of chemokines and cytokines such as CCL5 and XCL1 (“chemotactic dNK”), and a distinctive NK developmental program expressing CD44 and the transcription factor ZNF683 (Hobit).
Conclusion: Our data suggests that in fact, the dNK are not a homogeneous population and can be divided into at least two major phenotypes, with different roles and interactions with other cell types both immune and non-immune cells. Analysis of dNK at single cells resolution addresses a complex role for these immune cells in placental bed remodeling, immune surveillance and tolerance.
Figure1: 2D plot of ~30,000 sequenced immune cells from 20 1st trimester deciduas