Circulating Innate Lymphoid Cells Exhibit Distinctive Distribution During Normal Pregnancy

Yiran Zhao,Chengliang Zhou,Xi Chen,Zhiyang Zhou,Xinmei Liu,Yanhui Hao,Hefeng Huang,Hui Lin,Han Liu,Ningxin Qin,Li Jin,Yajie Zhu,Jianzhong Sheng

doi:10.1007/s43032-021-00834-6

Abstract

Over the past decades, the investigation of innate lymphoid cells (ILCs) has revealed their significance in successful pregnancy. Sex hormones, such as estradiol and progesterone, show specific changes during pregnancy and modulate both adaptive and innate immune systems. ILC subset distribution in peripheral blood of pregnant women and its potential association with sex hormone levels have not been well revealed. Peripheral blood was obtained from healthy non-pregnant, early-pregnant, and late-pregnant women. Radioimmunoassay was performed to measure plasma estradiol and progesterone levels. The levels of type 1 ILCs (ILC1s), type 2 ILCs (ILC2s), type 3 ILCs (ILC3s), and total ILCs as well as estrogen and progesterone receptors of ILC2s in peripheral blood were analyzed using flow cytometry. The proportion of total ILCs and distribution of ILC subsets in peripheral blood changed dynamically during pregnancy. Compared to non-pregnant women, late-pregnant women displayed significantly higher proportion of circulating ILCs, among which ILC2s accounted for the majority in late-pregnant women while a smaller part in others, and ILC3s displayed the opposite. Plasma estradiol and progesterone levels elevated while pregnancy proceeded and the expression of their receptors in ILC2s increased consisted with the proportion of circulating ILC2s. Our work first observed the existence of progesterone receptors in human circulating ILC2s and revealed the distribution pattern of circulating ILC subsets and their interrelation with plasma sex hormone levels during pregnancy. Our results suggested that the estradiol and progesterone levels might partly influence the distribution of circulating ILC subsets and implied the interplay between circulating ILCs and pregnancy.

Highlights

Successful pregnancy relies on the sophisticated balance of the immune system which maintains tolerance to the semiallogeneic fetus, while sustains innate and adaptability to meet challenges [1,2,3]
Our study aimed to explore the dynamic changes of helper type Innate lymphoid cells (ILCs) subsets before and during normal pregnancy, and whether plasma sex hormone levels correlate with ILC distribution in human peripheral blood
According to the diverse expression of transcriptional factors, helper ILCs have been divided into three subsets — Type 1 innate lymphoid cells (ILC1), Type 2 innate lymphoid cells (ILC2), and Type 3 innate lymphoid cells (ILC3), which are counterparts of T helper cells

Summary

Introduction

Successful pregnancy relies on the sophisticated balance of the immune system which maintains tolerance to the semiallogeneic fetus, while sustains innate and adaptability to meet challenges [1,2,3]. Recent studies have shown that T cells and their subgroups play a key role in preserving fetal development [4,5,6,7]. While the adaptive immune system plays an important role, the innate immune system matters [1, 8,9,10,11,12]. Innate lymphoid cells (ILCs) are a developing family of innate immune cells lacking lineage markers for T cells, B cells, myeloid and dendritic cells, monocytes and macrophages, mast cells, and stem cells and mirror the functions of T cells.

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Conclusion