MECHANISMS OF HORMONE-DRIVEN TRANSFORMATION OF NK CELLS IN PREGNANCY
DOI:
Keywords:
hormones of pregnancy, NK-cells, microRNA, granzymes, perforin, cytokines, inhibitory receptorsAbstract
The influence of reproductive hormones (HCG, estriol, kisspeptin, leptin, ghrelin) on phenotypic characteristics, cytokine production and the level of lytic activity of natural killer (NK) cells was studied. The role of miRNAs in the hormonal mechanisms of the formation of regulatory and cytotoxic subpopulations of NK cells during pregnancy was investigated.It was established that the reproductive hormones shift the balance of NK cells from cytotoxic subpopulation to the regulatory one. Herewith, the expression of the inhibitory molecule NKG2A and L-selectin was increased. The hormones at concentrations, corresponding to their levels during pregnancy, modulate cytokine spectrum, which is characteristic of regulatory NK3 subpopulation. The revealed action of hormones, manifested in the decrease of cytotoxic potential in the separated NK cells, in some cases was realized through the regulation of the level of the specific microRNAs.As a result of this work new physiological mechanisms of endocrine control of NK cells of the mother's immune system were identified, which could be implemented in different periods of pregnancy.
References
- Sirsev S.V. Immunologia materinsko-fetal’nyh vzaimodejstvij. - Ekaterinburg: UrO RAN, 2009. - 582 s.
- Hardie L., Trayhurn P., Abramovich D., Fowler P. Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy // Clin. Endocrinol. - 1997. - Vol. 47. - P. 101-106.
- Fuglsang J., Skjaerbaek C., Espelund U., Frystyk J., Fisker S., Flyvbjerg A., Ovesen P. Ghrelin and its relationship to growth hormones during normal pregnancy // Clin. Endocrinol. - 2005. - Vol. 62. - P. 554-559.
- Horikoshi Y., Matsumoto H., Takatsu Y., Ohtaki T., Kitada C., Usuki S., Fujino M. Dramatic elevation of plasma metastin concentrations in human pregnancy: metastin as a novel placenta-derived hormone in humans // J. Clin. Endocrinol. Metab. - 2003. - Vol. 2. - P. 914-919.
- Bulmer J.M., Johnson P.M. T cell apoptosis at the maternal-fetal interface in early human pregnancy, involvement of galectin-1 // Immunology. - 1985. - Vol. 55. - P. 35-44.
- Ashkar A.A., Di Santo J.P., Croy B.A. Interferon gamma contributes to initiation of uterine vascular modification, decidual integrity, and uterine natural killer cell maturation during normal murine pregnancy // J. Exp. Med. - 2000. - Vol. 192. - P. 259-270.
- Gong J., Liu R., Zhuang R. et al. miR-30c-1* promotes natural killer cell cytotoxicity against human hepatoma cells by targeting the transcription factor HMBOX1 // Cancer Sci. - 2012. - Vol. 103(4). - P. 645-652.
- Trotta R., Chen L., Ciarlariello D. [et al.] miR-155 regulates IFN-g production in natural killer cells // Blood. - 2012. - Vol. 119(15). - P. 3478-3485.
- Elemam N.M., Mekky R.Y., El-Ekiaby N.M. [et al.] Repressing PU.1 by miR-29a in NK cells of HCV patients, diminishes its cytolytic effect on HCV infected cell models // Hum. Immunol. - 2015. - Vol. 76. - P. 687-694.
- Wang P., Gu Y., Zhang Q. [et al.] Identification of resting and type I IFN-activated human NK cell miRNomes reveals microRNA-378 and microRNA-30e as negative regulators of NK cell cytotoxicity // J. Immunol. - 2012. - Vol. 189. - P. 211-221.
- Higuma-Myojo S., Sasaki Y., Miyazaki S. [et al.] Cytokine profile of natural killer cells in early human pregnancy // Am. J. Reprod. Immunol. - 2005. - Vol. 54. - P. 21-29.