**1. Introduction**

The emerging research topic called immunometabolism investigates mutual interactions between the immune system and the metabolism [1]. Chronic low-grade inflammation and disturbances in immune cell population participate in metabolic disorders such as non-alcoholic fatty liver disease,

type 2 diabetes mellitus, atherosclerosis, and metabolic syndrome [2]. Contrariwise, the dysfunctional remodeling of intracellular metabolic pathways plays a critical role for the functions of immune cells [3].

Dendritic cells (DCs) are the major antigen-presenting cells, which link the innate and adaptive immunity, maintaining tolerance to self-antigens. The human-derived DC family are typically classified into two phenotypically and functionally subsets, plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) [4]. In bloodstream, in vitro homologous monocyte-derived DCs (moDCs), require the influence of granulocyte/macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4) for differentiation [5]. Upon differentiation, moDCs undergo an activation process that, depending on their membrane receptors and secreted cytokines, means that moDCs may have either a pro-inflammatory or tolerogenic function. Pro-inflammatory activation is with CD80 and CD86 surface marker expression and IL-12p70 cytokine secretion, whereas PD-L1 and PD-L2 surface marker expression and IL-10 cytokine secretion are considered to prompt tolerogenic or anti-inflammatory activation of moDCs [6]. Any microenvironmental disturbance produces dysfunctional mDCs that may initiate inflammatory or autoimmune diseases. However, all the causes of mDC dysfunction have not been completely unraveled. One of the recognized causes is lipid accumulation, specifically triglycerides (TGs), in DCs from patients with cancer and autoimmune diseases, which may disturb DC function [7,8].

Owing to their hydrophobic nature, dietary fatty acids are transported in the form of postprandial TG-rich lipoproteins (TRLs, mainly chylomicrons) [9]. In healthy subjects, serum TG levels reach a peak over 1-3 h after eating a fatty meal, resulting in postprandial TRL accumulation in the bloodstream [10]. In previous studies, our research team has demonstrated the superiority of dietary oleic acid (i.e., monounsaturated fatty acid, MUFA) over palmitic and stearic acid (i.e., saturated fatty acids, SFAs) in buffering silent alterations postprandially [11–13]. Postprandial disturbances have been markedly interconnected with oxidative and inflammatory process linked to the differentiation and activation of circulating myeloid cells [14]. The binding of postprandial TRLs with their receptor, the ApoB48 receptor (ApoB48R), modulates TG accumulation in myeloid lineage [13,15], proposing that activation of immune cells may be the result of TRL uptake via ApoB48R. However, it is scarcely known whether dietary fatty acids in postprandial TRLs play a role in lipid accumulation in moDCs.

In this study, we assessed the potential role of TRLs rich in MUFAs (olive oil) without or with omega-3 long-chain polyunsaturated fatty acids (PUFAs)—olive oil + eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)—compared to TRLs rich in SFAs (cow's milk cream) in regulating moDC differentiation and whether dietary fatty acids are implicated in this process.
