The role of alpha-fetoprotein in the regulation of differentiation and functional activity of myeloid-derived suppressor cells

Abstract

Myeloid-derived suppressor cells (MDSC) are innate immune cells that suppress the immune response. MDSC levels increase in pathological conditions as well as during pregnancy. Alpha-fetoprotein (AFP) is synthesized by embryonic tissues and then enters the mother's bloodstream, where it performs both transport and immunomodulatory functions. However, its role in regulating MDSC development has not been studied. In this work, the effect of physiological concentrations of recombinant AFP (10, 50, 100 IU/mL) on the differentiation of human MDSC in the in vitro system was investigated. To work with MDSC, an experimental model was developed to obtain sufficient numbers of these cells by cytokine induction of myeloid cells (CD33+). It was found that AFP at concentrations of 50 and 100 IU/ml increased the total number of MDSC in culture. The detailed analysis subpopulations revealed that the increase was due to monocytic M-MDSC. Thus, for the first time, the direct effect of recombinant AFP on MDSC differentiation have been demonstrated for the first time, which makes it possible in the future to formulate a new concept for its action as a pharmacological drug.