Mesenchymal stem cells alter the frequency and cytokine profile of natural killer cells in abortion‐prone mice

Abstract

Natural killer cells, which play a pivotal role in the establishment and maintenance of normal pregnancy, are the most abundant leukocytes at the fetomaternal interface that their subsets frequencies and cytokine profile are influential factors in the preservation of the decidual tolerogenic microenvironment. Any imbalance in NK cells' frequency and functions could be associated with pregnancy failure.Mesenchymal stem cells (MSCs) are shown to have immunomodulatory effects on NK cells and their cytokine profile. The purpose of this study is to evaluate the impact of MSCs therapy on the cytokine profiles and subpopulations of NK cells in a murine model of recurrent pregnancy loss. Adipose-derived MSCs were injected intraperitoneally to the abortion-prone mice on Day 4.5 of gestation. The abortion rate was determined after MSCs administration and the frequency and cytokine profiles of the different subsets of NK cells were determined using the flow cytometry. Our results showed that, in abortion-prone mice, the frequency of CD49b + NK cells was significantly higher than normal pregnant mice that decreased after therapy. We also demonstrated that MSCs downregulated the production of IFN-γ and upregulated IL-4 and IL-10 production by uNK cells. These findings indicate that MSCs can decrease the infiltration of CD49b + NK cells to the fetomaternal interface and modulate the cytokine profile of NK cells from inflammatory to tolerogenic profile and thereby improve the tolerogenic microenvironment at the fetomaternal interface in benefit of pregnancy maintenance.

The Immunomodulatory Properties of Mesenchymal Stem Cells Play a Critical Role in Inducing Immune Tolerance after Liver Transplantation

“…Moreover, MSCs cannot only effectively inhibit IL-2-induced NK cell proliferation but also prevent cytotoxic activity and cytokine production. Notably, indoleamine 2,3-dioxygenase (IDO) and prostaglandin E2 (PGE2) were reported to be the key mediators in MSC-induced inhibition of NK cells [ 73 , 74 ].…”

A Brief Analysis of Tissue-Resident NK Cells in Pregnancy and Endometrial Diseases: The Importance of Pharmacologic Modulation

“…The structures contain protein, DNA, RNA, and/or miRNA of the cells that secrete them. Exosomes have been used as biomarkers in different reproductive diseases [145][146][147][148][149][150][151].…”

“…The use of endosomes for therapy has raised the interest of several groups in recent years [145][146][147][148][149]. In addition, the experience with other disease has provided new tools for generating individual and targeted analysis to decrease the inflammatory response and provide the critical tissue milieu for implantation and pregnancy [145][146][147][148][149][150][151].…”

The role of decidual natural killer cell‐derived soluble factors in early pregnancy

“…For instance, a study revealed that dNK extracted from patients with preeclampsia (PE) express high levels of intracellular IFNγ and that culture medium (CM) can inhibit trophoblasts migration and invasion 26 . Similarly, in miscarriage‐prone mice, IFNγ + NKs are more frequently detected in the decidua compared with those with healthy pregnancies 27 . Hence, the immunotolerant role of IFNγ in pregnancy appears to be paradoxical, warranting further investigation into the underlying mechanism.…”