Toll-like receptor signaling in uterine natural killer cells--role in embryonic loss.
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.
Lin
Yi
Y
Institute of Obstetrics and Gynecology, Department of Obstetrics and Gynecology, Renji Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, PR China. yilinonline@gmail.com
Nakashima
Akitoshi
A
Shima
Tomoko
T
Zhou
Xing
X
Saito
Shigeru
S
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis; D000943:Antigens, Differentiation / Q000096:biosynthesis; D005260:Female; D005313:Fetal Death / Q000276:immunology* / Q000517:prevention & control; D006801:Humans; D056747:Immunomodulation; D016753:Interleukin-10 / Q000276:immunology; D007694:Killer Cells, Natural / Q000502:physiology*; D051379:Mice; D011247:Pregnancy; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000502:physiology; D051193:Toll-Like Receptors / Q000502:physiology*; D014599:Uterus / Q000473:pathology / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D051193:Toll-Like Receptors; D016753:Interleukin-10