Abstract
The effects of kisspeptin, an important regulator of reproductive function, and leptin, a classical metabolic hormone, on the formation of inducible regulatory T cells (iTreg) and T helper cells that produce interleukin 17 (Th17), as well as on the activity of indoleamine 2,3-dioxygenase (IDO) have been studied. Both hormones are actively produced by the placenta and involved in the formation of a new hormonal profile during pregnancy. It was found that kisspeptin at concentrations typical for trimesters I–III of pregnancy stimulates the formation of iTreg and simultaneously inhibit Th17 induction. Regardless of the used concentration, kisspeptin increases the secretion of interleukin-10 (IL-10) and reduces the production of IL-17A in CD4+ T lymphocytes in women. At the same time leptin at physiological concentrations typical for pregnancy has the opposite effect, inhibiting the formation of iTreg without affecting the production of IL-10 in cultures of CD4+T lymphocytes and simultaneous stimulating the induction of Th17 and production of IL-17A in CD4+T lymphocytes. At the concentration corresponding to trimesters II–III of pregnancy both hormones significantly enhance lipopolysaccharide-induced activity of IDO in monocytes.
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References
Shirshev, S.V., Immunologiya materinsko-fetal’nykh vzaimodeistvii (Immunology of Maternal-Fetal Interactions), Yekaterinburg: Ural. Otd., Ross. Akad. Nauk, 2009.
Garcia-Garcia, R.M., Integrative control of energy balance and reproduction in females, ISRN Vet. Sci., 2012, vol. 2012, p.51.
Tena-Sempere, M., Interaction between energy homeostasis and reproduction: central effects of leptin and ghrelin on the reproductive axis, Horm. Metab. Res., 2013, vol. 45, p.919.
Hill, J., Elmqust, J., and Elias, C., Hypothalamic pathways linking energy balance and reproduction, Am. J. Physiol. Endocrinol. Metab., 2008, vol. 294, p.827.
Pompolo, S., Pereira, A., Estrada, K., and Clarke, I., Colocalization of kisspeptin and gonadotropin-releasing hormone in the ovine brain, Endocrinology, 2006, vol. 147, p.804.
Dhillo, W.S., Murphy, K.G., and Bloom, S.R., The neuroendocrine physiology of kisspeptin in the human, Rev. Endocrinol. Metab. Disord., 2007, vol. 8, p.41.
Mellor, A.L. and Munn, D.H., Tryptophan catabolism prevents maternal T cells from activating lethal antifetal immune responses, J. Reprod. Immunol., 2001, vol. 52, p.5.
Liu, Y.S., Wu, L., Tong, X.H., et al., Study on the relationship between Th17 cells and unexplained recurrent spontaneous abortion, Am. J. Reprod. Immunol., 2011, vol. 65, p.503.
Ohtaki, T., Shintani, Y., Honda, S., et al., Metastasis suppressor gene KiSS-1 encodes peptide ligand of a Gprotein-coupled receptor, Nature, 2001, vol. 411, p.613.
Matarese, G., Carrieri, P.B., La Cava, A., et al., Leptin increase in multiple sclerosis associates with reduced number of CD4(+)CD25(+) regulatory T cells, Proc. Natl. Acad. Sci. U.S.A., 2005, vol. 102, p. 5150.
Koshiba, H., Kitawaki, J., Ishihara, H., et al., Progesterone inhibition of functional leptin receptor mRNA expression in human endometrium, Mol. Hum. Reprod., 2001, vol. 7. № 6, p.567.
Horikoshi, Y., Matsumoto, H., Takatsu, Y., et al., 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.
Hardie, L. and Trayhurn, P., Circulating leptin in women: longitudinal study in menstrual cycle and during pregnancy, Clin. Endocrinol., 1997, vol. 47, p.101.
Ichiyama, K., Yoshida, H., Wakabayashi, Y., et al., Foxp3 inhibits RORgammat-mediated IL-17A mRNA transcription through direct interaction with RORgammat, J. Biol. Chem., 2008, vol. 283, p. 17003.
Ephrem, A., Epstein, A. L., Stephens, G.L., et al., Modulation of Treg cells/T effector function by GITR signaling is context-dependent, Eur. J. Immunol., 2013, vol. 43, p. 2421.
Acosta-Rodriguez, E.V., Napoletani, G., Lanzavecchia, A., and Sallusto, F., Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells, Nat. Immunol., 2007, vol. 8, p.942.
Braun, D., Longman, R.S., and Albert, M.L., A twostep induction of indoleamine 2.3 dioxygenase (IDO) activity during dendritic-cell maturation, Blood, 2005, vol. 106, p. 2375.
Zheng, Y., Manzotti, C., Burke, F., et al., Acquisition of suppressive function by activated human CD4+ CD25-T cells is associated with the expression of CTLA-4 not FoxP3, J. Immunol., 2008, vol. 181, p. 1683.
Gu, Y., Yang, J., Ouyang, X., et al., Interleukin 10 suppresses Th17 cytokines secreted by macrophages and T cells, Eur. J. Immunol., 2008, vol. 38, p. 1807.
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Original Russian Text © S.V. Shirshev, O.L. Gorbunova, E.G. Orlova, 2017, published in Fiziologiya Cheloveka, 2017, Vol. 43, No. 6, pp. 109–114.
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Shirshev, S.V., Gorbunova, O.L. & Orlova, E.G. Role of Kisspeptin and Leptin in the Development of Immune Reactivity during Pregnancy. Hum Physiol 43, 705–710 (2017). https://doi.org/10.1134/S0362119717060111
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DOI: https://doi.org/10.1134/S0362119717060111