Mechanisms of Leptin and Ghrelin Action on Maturation and Functions of Dendritic Cells

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E. G. Orlova^1,a*, S. V. Shirshev¹, and O. A. Loginova¹

¹Perm Federal Research Center, Institute of Ecology and Genetics of Microorganisms, Ural Branch of the Russian Academy of Sciences, 614081 Perm, Russia

^* To whom correspondence should be addressed.

Received July 3, 2018; Revised September 17, 2018; Accepted September 17, 2018

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Molecular mechanisms of the immunomodulatory effects of leptin and ghrelin in concentrations typical for pregnancy on the maturation and functional activity of dendritic cells (DCs) generated from the peripheral blood monocytes of women are investigated. The presence of leptin during DC maturation did not affect the levels of CD83⁺CD1c⁺, CD86⁺CD1c⁺, and HLA-DR⁺CD1c⁺ DCs, but increased the amount and the activity of the enzyme indoleamine 2,3-dioxygenase (IDO). Cell culturing in the presence of ghrelin or combination of leptin and ghrelin reduced the percentage of CD86⁺CD1c⁺ DCs but did not affect the levels of CD83⁺CD1c⁺ and HLA-DR⁺CD1c⁺ DCs. In addition, ghrelin reduced the number of IDO molecules without affecting its activity. Simultaneous presence of leptin and ghrelin increased induced IDO activity without affecting the amount of the enzyme in DCs. The effects of leptin and ghrelin on the investigated functions of DCs in some cases correlated with high levels of cAMP. New mechanisms for leptin and ghrelin regulation of tolerogenic functions of DCs in pregnancy are proposed.

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KEY WORDS: leptin, ghrelin, pregnancy, dendritic cells, IDO, cAMP

DOI: 10.1134/S0006297919010012

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