Developing dendritic cells become ‘lacy’ cells packed with fat and glycogen

Abstract

SummaryOn maturation, dendritic cells (DCs) become highly active cells equipped for antigen uptake, migration and clustering and activation of T cells. We therefore asked whether DCs acquire fat and glycogen stores as they mature. DCs were generated from mouse bone marrow stem cells by culturing with granulocyte-macrophage colony-stimulating factor (GM-CSF) for 7-8 days. Stimulation of the DCs with lipopolysaccharide (LPS) for the last 24 hr of culture, or exposure to 1-15 ng/ml of interleukin (IL)-4 during development, resulted in production of DCs not only with an increased ability to stimulate T cells but also with an increasingly lacy appearance on transmission electron microscopy, with multiple unstained areas in the cytoplasm. This changed morphology was associated with the presence of increasing amounts of fat and glycogen, identified by Sudan Black and periodic acid leukofushin/Schiff (PAS) staining, respectively. Lacy DCs up-regulated type 1 and type 2 scavenger receptors, providing possible mechanisms contributing to these changes. Lacy DCs were found occasionally amongst freshly isolated splenic and lymph node DCs. DCs can be isolated from human adipose tissue, and we tested whether lacy DCs acquiring fat and glycogen were present in mouse omentum. CD45 + cells migrating from the omentum expressed specific DC markers CD11c and 33D1, costimulatory molecules and major histocompatibility complex (MHC) class II, and most showed darkly staining fat inclusions. Thus, during development, DCs can acquire large amounts of fat and glycogen, accumulation of which is promoted by antigen exposure and modulated by the cytokine milieu and location, and which may act as a link between energy stores and immune function.

Obesity, pregnancy, inflammation, and vascular function

“…A similar placental phenotype has recently been reported in a baboon model of obesity (Farley et al 2009). It is also possible that maternal obesity may affect the number and function of other immune cell populations (Weisberg et al 2003, Maroof et al 2005, Macia et al 2006 at the maternal-fetal interface including natural killer cells and dendritic cells. Alterations in these cell populations could have lifelong implications for the fetal acquired immune system and disease susceptibility in later life (Challier et al 2008).…”

Flt3 ligand generates morphologically distinct semimature dendritic cells in ovalbumin-sensitized mice

“…However the spleen plasmacytoid DCs contain very few well developed mitochondria and almost no rough endoplasmic reticulum (Figure 5 Panel B). In addition myeloid DCs from both lungs and spleen of OVA sensitized and challenged mice showed fat and glycogen stores which are typical characteristic of mature DCs (Maroof et al, 2005). Increased presence of mitochondria and rough endoplasmic reticulum indicates heightened cellular activity.…”

Lymphocytes in the Peritoneum Home to the Omentum and Are Activated by Resident Dendritic Cells

“…These stimulatory CD11c high MHC-II high CD19/B220 Ϫ cells therefore exhibit both functional and phenotypic hallmarks of conventional DCs (51,52). DCs were recently identified in older human omenta (17 adult donors aged 25-69 years, mean age of 53 years) (19), but walkout cells from omenta of 6-to 8-wk-old mice reportedly failed to stimulate in mixed lymphocyte reactions despite exhibiting some phenotypic properties of DCs (20). This discrepancy with our observations might have occurred if macrophages, or other myeloid cells with inhibitory activity in mixed lymphocyte reactions, were more prevalent in OFB of mice used in the latter study relative to mice used in our study.…”

“…The rapid onset of CD69 expression described above indicated that Ag-presenting DCs might be present in the omentum, although previous studies have suggested that the omentum lacks DCs (8) based on both phentoypic (5, 9) and functional criteria (20). We therefore assessed the Ag presentation capabilities of OFB resident cells for their ability to activate naive allogeneic or male peptidespecific T cells.…”