PBX1 expression in uterine natural killer cells drives fetal growth

Yonggang Zhou; Binqing Fu; Xiuxiu Xu; Jinghe Zhang; Xianhong Tong; Yanshi Wang; Zhongjun Dong; Xiaoren Zhang; Nan Shen; Yiwen Zhai; Xiangdong Kong; Rui Sun; Zhigang Tian; Haiming Wei

doi:10.1126/scitranslmed.aax1798

PBX1 expression in uterine natural killer cells drives fetal growth

Sci Transl Med. 2020 Apr 1;12(537):eaax1798. doi: 10.1126/scitranslmed.aax1798.

Authors

Yonggang Zhou^{1

2

3}, Binqing Fu^{4

2}, Xiuxiu Xu^{1

2}, Jinghe Zhang^{1

2}, Xianhong Tong³, Yanshi Wang³, Zhongjun Dong⁵, Xiaoren Zhang⁶, Nan Shen⁷, Yiwen Zhai⁸, Xiangdong Kong⁸, Rui Sun^{1

2}, Zhigang Tian^{4

2}, Haiming Wei^{4

2}

Affiliations

¹ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China.
² Institute of Immunology, University of Science and Technology of China, Hefei, Anhui 230027, China.
³ First Affiliated Hospital, University of Science and Technology of China, Hefei, Anhui 230026, China.
⁴ Division of Molecular Medicine, Hefei National Laboratory for Physical Sciences at Microscale, The CAS Key Laboratory of Innate Immunity and Chronic Disease, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230027, China. ustcwhm@ustc.edu.cn tzg@ustc.edu.cn fbq@ustc.edu.cn.
⁵ School of Medicine, Tsinghua University, Beijing 100086, China.
⁶ CAS Key Laboratory of Tissue Microenvironment and Tumor, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200025, China.
⁷ Shanghai Institute of Rheumatology, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200001, China.
⁸ Center for Genetic and Prenatal Diagnosis, Department of Gynecology and Obstetrics, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.

PMID: 32238574
DOI: 10.1126/scitranslmed.aax1798

Abstract

Abundant decidual natural killer (dNK) cells at the maternal-fetal interface are important during early pregnancy. However, functional subsets of dNK cells remain poorly understood. We describe a CD49a⁺PBX homeobox 1 (PBX1)⁺ dNK cell subset that promotes fetal development in humans and mice. The expression of PBX1 in dNK cells is up-regulated via the activated AKT1 pathway through the interaction of major histocompatibility complex G with the immunoglobulin-like transcript 2 receptor. PBX1 drives pleiotrophin and osteoglycin transcription in dNK cells, further promoting fetal development. Decreased PBX1 expression or the PBX1^G21S mutant correlated with fetal growth restriction and pregnancy failure in patients with unexplained recurrent spontaneous abortion (URSA). Inactivation of Pbx1 in mouse dNK cells impairs fetal development by decreasing growth-promoting factors from CD49a⁺PBX1⁺ dNK cells. Impairment of PBX1 in dNK cells has positive correlation with URSA pathogenesis and may provide a potential marker for this condition.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Decidua* / metabolism
Female
Fetal Development*
Humans
Intercellular Signaling Peptides and Proteins
Killer Cells, Natural*
Mice
Pregnancy
Uterus

Substances

Intercellular Signaling Peptides and Proteins