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

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−CD56bright 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−CD56bright 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.

Keywords: Immune modulation, Immune tolerance, Pregnancy, Toll-like receptor, uNK cells

a Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200001, PR China

b Department of Obstetrics and Gynecology, Faculty of Medicine, University of Toyama, Toyama 930-0194, Japan

Corresponding author. Tel.: +86 21 50390870; fax: +86 21 50390610.

Corresponding author. Tel.: +81 76 434 7355; fax: +81 76 434 5036.

PII: S0165-0378(09)00478-1

doi:10.1016/j.jri.2009.09.004

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