Dietary Glucose Consumption Promotes RALDH Activity in Small Intestinal CD103+CD11b+ Dendritic Cells

Abstract

Retinal dehydrogenase (RALDH) enzymatic activities catalyze the conversion of vitamin A to its metabolite Retinoic acid (RA) in intestinal dendritic cells (DCs) and promote immunological tolerance. However, precise understanding of the exogenous factors that act as initial trigger of RALDH activity in these cells is still evolving. By using germ-free (GF) mice raised on an antigen free (AF) elemental diet, we find that certain components in diet are critically required to establish optimal RALDH expression and activity, most prominently in small intestinal CD103 + CD11b + DCs (siLP-DCs) right from the beginning of their lives. Surprisingly, systematic screens using modified diets devoid of individual dietary components indicate that proteins, starch and minerals are dispensable for this activity. On the other hand, in depth comparison between subtle differences in dietary composition among different dietary regimes reveal that adequate glucose concentration in diet is a critical determinant for establishing RALDH activity specifically in siLP-DCs. Consequently, pre-treatment of siLP-DCs, and not mesenteric lymph node derived MLNDCs with glucose, results in significant enhancement in the in vitro generation of induced Regulatory T (iTreg) cells. Our findings reveal previously underappreciated role of dietary glucose concentration in establishing regulatory properties in intestinal DCs, thereby extending a potential therapeutic module against intestinal inflammation.

Ovalbumin-Induced Epithelial Activation Directs Monocyte-Derived Dendritic Cells to Instruct Type 2 Inflammation in T Cells Which Is Differentially Modulated by 2′-Fucosyllactose and 3-Fucosyllactose

“…The observed increased secretion of the chemoattractants CCL20 and IL8 is known to recruit innate immune cells, including DC, to the site of inflammation [9]. Elevated levels of galectin-9, TGFβ, and RALDH are part of maintaining this mucosal homeostasis by inducing Treg formation [23,[28][29][30]. Upon OVA exposure, TGFβ levels were increased, while galectin-9 and RALDH levels were not affected.…”

Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

“…This is especially interesting in light of growing evidence that microbiota-dependent signals cause autoreactive T cells to trigger uveitis ( Horai et al, 2015 ), which makes it tempting to speculate that gut-resident cDC2 subsets contribute to the activation of T cells in uveitis models. Dietary components can influence subsets of intestinal dendritic cells ( Ko et al, 2020 ). Regardless, most likely, an ensemble of disease modulating factors is involved.…”

Transcriptome network analysis implicates CX3CR1-positive type 3 dendritic cells in non-infectious uveitis

“…This is especially interesting in light of growing evidence that microbiota dependent signals cause autoreactive T cells to trigger uveitis ( 66 ), which makes it tempting to speculate that gut-resident cDC2 subsets contribute to the activation of T cells in uveitis models. Dietary components can influence subsets of intestinal dendritic cells ( 67 ). Regardless, most likely, an ensemble of disease modulating factors is involved.…”