A subset of human pancreatic beta cells express functional CD14 receptors: a signaling pathway for beta cell‐related glycolipids, sulfatide and β‐galactosylceramide

Abstract

A subset of human beta-cells expresses functional CD14 receptor and thus is able to recognize both exogenous bacterial (LPS) as well as endogenous ligands (e.g. glycolipids of beta-cell origin). The CD14 expression on a subset of human beta-cells may play a role in the innate surveillance of the endocrine environment but may also contribute to innate immune mechanisms in the early stages of beta-cell aggression.

Roles of ceramide and sphingolipids in pancreatic β-cell function and dysfunction

“…Moreover, C16:0 sulfatide significantly improves insulin crystal preservation 99 . As discussed earlier, the co-secretion of sulfatide with insulin also appears to negatively regulate CD14 signaling to prevent excessive secretion of pro-inflammatory cytokines from the β-cell that may precipitate β-cell destruction 28 . Collectively these studies make a strong case for sulfatide playing an important role in β-cell biology, and this is another topic for reinvestigation using newer genetic and analytical tools.…”

“…One such is the macrophage scavenger receptor, CD14, which is primarily expressed on monocytes, macrophages and other immune cell types with lipopolysaccharide (LPS) as its natural ligand. CD14 is also expressed on a subset of β-cells from human islets 28 . In addition to LPS, GalCer, acting via the CD14 receptor and presumably in an auto/paracrine manner, was also found to also stimulate β-cells to secrete TNF-α, IL-1β and IL-8.…”

“…In addition to LPS, GalCer, acting via the CD14 receptor and presumably in an auto/paracrine manner, was also found to also stimulate β-cells to secrete TNF-α, IL-1β and IL-8. Conversely sulfatide, another endogenous glycolipid found in insulin secretory granules, inhibited LPS effects mediated via the CD14 receptor 28 . However, the real physiological role of CD14 on the β-cell surface and whether it contributes to β-cell death seen in diabetes is as yet unclear.…”

Maintenance of β-Cell Maturity and Plasticity in the Adult Pancreas

“…Heterogeneity may be linked to differential susceptibility to death under conditions of type 1 diabetes (33) or stress induced by misfolded insulin proteins (34). The observation of heterogeneity can be interpreted as independent subpopulations of β-cells that stably express different amounts of insulin.…”

Chimeric Anti-CD14 IGG2/4 Hybrid Antibodies for Therapeutic Intervention in Pig and Human Models of Inflammation

“…It is a cofactor of TLRs 2, 3, 4, 7, and 9 in mouse and TLRs 2, 4, and 9 in humans (4) and thus involved in the recognition of a variety of pathogen-or damage-associated molecular patterns. A number of exogenous and endogenous CD14 ligands have been identified, mostly being acylated structural components such as lipopeptides and glycolipids (5)(6)(7). Thus, CD14 is a multifunctional, upstream regulator of innate immune function and is therefore an attractive target for directed inhibition of a broad spectrum of inflammatory threats such as sepsis, ischemia reperfusion injury, and trauma-or burn-induced systemic inflammatory response syndrome.…”