Alpha-Fetoprotein as a Factor of Differentiation and Functional Activity of Myeloid-Derived Suppressor Cells

• Published in: Bulletin of experimental biology and medicine Vol. 175; no. 4; pp. 535 - 543
• Main Authors: Shardina, K. Yu, Zamorina, S. A., Timganova, V. P., Bochkova, M. S., Uzhviyuk, S. V., Chereshnev, V. A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.08.2023; Springer; Springer Nature B.V
• Subjects: APRIL protein; Arginase; Biomedical and Life Sciences; Biomedicine; CD11b antigen; Cell Biology; Cytokines; Gelatinase A; Glycoproteins; Granulocyte-macrophage colony-stimulating factor; Internal Medicine; Laboratory Medicine; Monocytes; Pathology; Peripheral blood; Phenotypes; Pregnancy; Suppressor cells; Tryptophan 2,3-dioxygenase; α-Fetoprotein; cytokines; myeloid-derived suppressor cells (MDSC); alpha-fetoprotein; CD11b; pregnancy
• ISSN: 0007-4888; 1573-8221
• DOI: 10.1007/s10517-023-05901-3

We studied the role of alpha-fetoprotein (AFP) in regulation of differentiation and functional activity of human myeloid-derived suppressor cells (MDSC) in vitro . To obtain MDSC, CD11b + cells were isolated from the peripheral blood of healthy donors followed by cytokine induction (IL-1β+GM-CSF) into the MDSC phenotype. The cell functions were assessed by the expression of indoleamine 2,3-dioxygenase (IDO) and arginase-1 (Arg1) and cytokine profile of the cell cultures. Native AFP did not affect the total number of MDSC and the percentage of polymorphonuclear MDSC (PMN-MDSC), but increased the number of monocytic MDSC (M-MDSC). AFP did not change the expression of Arg1, but in low concentrations (10 and 50 U/ml) increased the number of IDO-containing cells. AFP modulated the cytokine profile of CD11b + cells: it reliably decreased the level of IL-19 (50 and100 U/ml) and showed a tendency to decrease the levels of IL-34, MMP-2, sCD163, CHI3L1, OPN and to increase the levels of IL-29, IL-32, APRIL, PTX3, and sTNF-R1. Thus, we have demonstrated a regulatory effect of native AFP at the level of MDSC generated from CD11b + cells under conditions of cytokine induction in vitro .