Supplementary material to "Glutamine metabolism shapes the phenotypic adaptation of uterine dendritic cells in response to early allogeneic pregnancy"

Supplementary material to "Glutamine metabolism shapes the phenotypic adaptation of uterine dendritic cells in response to early allogeneic pregnancy"

ABSTRACT

The impact of metabolic reprogramming on immune cell functions is increasingly recognized. However, it remains largely unexplored in terms of immune cells adaptation during reproduction. Dendritic cells (DC) are crucial for establishing and maintaining pregnancy by orchestrating maternal immune adaptation essential for embryo implantation and decidualization. Here, we characterized the phenotypic and metabolic characteristics of DCs during early pregnancy in an allogeneic mouse model and in response to the specific deletion of hormonal receptors on DCs. Frequency of uterine CD11c⁺ DCs on gestational day (gd) 7.5 remained equal to that of non-pregnant mice. However, we observed a functional shift from cDC1 to cDC2 in pregnant mice. In parallel, a metabolic switch in uterine DCs was identified by upregulation of genes representing fatty acid synthesis (<em>Fasn</em>, <em>Acaca</em>), fatty acid oxidation (<em>Cpt1a</em>), and glutamine-related metabolic pathways (<em>Got2</em>). The cell-specific deletion of the glucocorticoid receptor in DCs reduced their MHCII expression, accompanied by a reduction in <em>Got2</em> expression. Glutamine deprivation i<em>n vitro</em> dramatically reduced the absolute number of cultured bone marrow cells and the frequency of cDC1s while simultaneously increasing the frequency of cDC2s. Collectively, these findings establish glutamine metabolism as a key driver of DC adaptation during early pregnancy, revealing novel metabolic-immunological crosstalk at the maternal-fetal interface.