Trophoblast-derived CXCL16 induces M2 macrophage polarization that in turn inactivates NK cells at the maternal\u2013fetal interface

Xiao-Qiu Wang,Wen-Jie Zhou,Da-Jin Li,Qiang Fu,Xin-Xin Hou

doi:10.1038/s41423-018-0019-x

Abstract

Decidual macrophages (dMΦ) are distinct from the conventional macrophages present in other tissues and express M2 macrophage markers, but the molecular mechanisms of formation and the roles of M2 MΦ during pregnancy have not been completely elucidated. The crosstalk between decidual natural killer cells (dNK) and dMΦ plays an important role in the maintenance of maternal–fetal immune tolerance. Here, CXCL16 derived from first-trimester trophoblast cells induces the polarization of human M2 macrophages. The M2 MΦ polarized by CXCL16 exhibit decreased interleukin-15 production, which facilitates the inactivation of NK cells. The cytotoxicity of NK cells is attenuated by the CXCL16-polarized M2 MΦ. The data shown in the present study provide evidence to support the hypothesis that CXCL16 secreted by trophoblast cells is a key molecule involved in decidual M2 MΦ polarization, which in turn regulates the killing ability of NK cells, thereby contributing to the homeostatic and immune-tolerant milieu required for successful fetal development.

Highlights

In a successful pregnancy, the allogeneic fetoplacental unit is not rejected by the maternal immune system, and the mechanisms involved in this process are critically important
Cells were washed once with 1 ml of PBS by We investigated whether the CXCL16 secreted by primary centrifugation at 1500 r.p.m. for 8 min and analyzed using a trophoblast cells would induce the expression of M2 macrophage
CXCL16-polarized M2 MΦ facilitate the inactivation of natural killer (NK) cells We examined whether M2 MΦ polarized by CXCL16 influenced NK cell activation to further clarify the role of CXCL16-polarized MΦ in maternal–fetal immune tolerance

Summary

Introduction

The allogeneic fetoplacental unit is not rejected by the maternal immune system, and the mechanisms involved in this process are critically important. A large and specific population of immune cells is located in the decidua. These decidual leukocytes (DLC) play important roles in local cytokine production, reducing cytotoxicity, vascularization, and placental development to maintain a healthy pregnancy.[1,2]. The number of uterine leukocytes dramatically increases during decidualization and displays an unusual composition: approximately 70% are cluster of differentiation CD56brightCD16– natural killer (NK) cells, and the remainder include macrophages (MΦ) and T cells.[3,4] These cells play important roles in the establishment and maintenance of maternal–fetal immune tolerance. CXCL16 secreted by the fetus-derived trophoblasts stimulates MΦ by interacting with its receptor CXCR6 on the macrophage surface, potentially leading to the formation of a specific immune microenvironment at the maternal–fetal interface.[5] CXCL16 is expressed as both transmembrane and soluble forms

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