Sulfatide-reactive type II NKT cells have been shown to regulate autoimmunity and anti-tumor immunity. Although, two major isoforms of sulfatide, C16:0 and C24:0, are enriched in the pancreas, their relative role in autoimmune diabetes is not known. Here, we report that sulfatide/CD1d-tetramer+ cells accumulate in the draining pancreatic lymph nodes, and that treatment of NOD mice with sulfatide or C24:0 was more efficient than C16:0 in stimulating the NKT cell-mediated transfer of a delay in onset from T1D into NOD.Scid recipients. Using NOD.CD1d−/− mice, we show that this delay of T1D is CD1d-dependent. Interestingly, the latter delay or protection from T1D is associated with the enhanced secretion of IL-10 rather than IFN-g by C24:0-treated CD4+ T cells and the deviation of the islet-reactive diabetogenic T cell response. Both C16:0 and C24:0 sulfatide isoforms are unable to activate and expand type I iNKT cells. Collectively, these data suggest that C24:0 stimulated type II NKT cells may regulate protection from T1D by activating DCs to secrete IL-10 and suppress the activation and expansion of type I iNKT cells and diabetogenic T cells. Our results raise the possibility that C24:0 may be used therapeutically to delay the onset and protect from T1D in humans.
BackgroundSmall, dense low-density lipoprotein (sd-LDL) and glycated LDL (g-LDL) have been associated with cardiovascular disease (CVD) in chronic kidney disease (CKD) in patients >60 years of age. Since young adult and paediatric patients have shorter exposure to Framingham-type risk factors, our study aims to determine whether younger CKD patients exhibit the same sd-LDL and g-LDL pattern.MethodsAfter ethics board approval, this cross-sectional study was conducted at two universities with 44 patients (mean ± standard deviation age 12.6 ± 4.9, range 2–24 years) with CKD stage of 1–5. Laboratory parameters studied were Cystatin C (CysC), CysC estimated glomerular filtration rate (eGFR) (calculated from the Filler formula), sd-LDL, g-LDL and albumin. Lipid samples were measured for sd-LDL and g-LDL using ELISA. Non-linear correlation analysis was performed to determine the relationship between g-LDL, sd-LDL and eGFR. Clinical Trials Registration is at clinicaltrials.gov, NCT02126293, https://clinicaltrials.gov/ct2/show/NCT02126293.ResultsTriglycerides, but not total cholesterol and calculated LDL, were associated with CKD stages (ANOVA P = 0.0091). As in adults, sd-LDL was significantly associated with CKD stages (ANOVA P = 0.0133), CysC eGFR (r = −0.6495, P < 0.00001), and body mass index (r = −0.3895, P = 0.0189), but not with age. By contrast, there was no significant correlation between g-LDL and CKD stages or CysC eGFR (P = 0.9678).ConclusionsOur study demonstrates that only triglycerides and sd-LDL were associated with CKD stages in this young cohort without confounding Framingham-type CVD risk factors. While larger studies are needed, this study suggests that lowering sd-LDL levels may be a potential target to ameliorate the long-term CVD risks in paediatric CKD patients.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.