Toll-like receptor signaling in uterine natural killer cells—role in embryonic loss

Lin, Yi; Nakashima, Akitoshi; Shima, Tomoko; Zhou, Xing; Saito, Shigeru

doi:10.1016/j.jri.2009.09.004

« Previous Next »Journal of Reproductive Immunology
Volume 83, Issue 1 , Pages 95-100, December 2009

Toll-like receptor signaling in uterine natural killer cells—role in embryonic loss

Yi Lin
- Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, PR China
- Corresponding author. Tel.: +86 21 50390870; fax: +86 21 50390610.
Akitoshi Nakashima
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan
Tomoko Shima
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan
Xing Zhou
- Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, PR China
Shigeru Saito
- Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan
- Corresponding author. Tel.: +81 76 434 7355; fax: +81 76 434 5036.

Received 25 April 2009; received in revised form 22 August 2009; accepted 7 September 2009. published online 23 October 2009.

Abstract

Embryonic development is a complex process that is regulated by many cell types and signaling pathways. This review focuses on the role of NK cells and regulatory T-cells (Treg cells) in embryonic loss. Approximately 70% of uterine leukocytes until the time of mid-gestation are found to be CD16⁻CD56^bright NK cells. This subset of NK cells, along with Treg cells, has been shown to regulate fetal development. We recently found a population of NK cells in the pregnant mouse uterus with a unique CD3⁻CD49b⁺CD25⁺Foxp3⁺ phenotype. This review summarizes the studies indicating critical roles for expression of IL-10 by CD3⁻CD49b⁺CD25⁺Foxp3⁺ cells and CXCR4 expression on CD16⁻CD56^bright NK cells in preventing embryonic loss. In addition, the roles of toll-like receptors (TLRs) and CXCR4 in NK cell migration and functional modulation are discussed.