Genetic Studies in 5 Greek Population Samples Using 12 Highly Polymorphic DNA Loci

Two minisatellite (D1S80, D17S5) and 10 microsatellite (.D2S1328, TPO, D3S1358, D9S926, DUS2010, THOl, VWF, FES, D16S310, and D18S848) polymorphic loci were analyzed in 5 Greek population groups (eastern Macedonia, central Macedonia, Thessaly, Epirus, and Greeks from Asia Minor) using the polymerase chain reaction. The genotypes at these loci conformed to Hardy-Weinberg equilibrium, and pairwise comparisons between them were in agreement with the expectation of independence between loci. This along with the low values of the coefficient of gene differentiation (GST) and the high heterozygosity levels of all loci allows the use of allele frequency data from the 12 hypervariable DNA markers for medicolegal casework in the Greek population groups studied. The small genetic distances indicate a genetic affinity among the 5 population samples. However, a few markers seem to allow some discrimination among the groups. No significant differences with other European populations were found for the loci studied

Obesity Reduces mTORC1 Activity in Mucosal-Associated Invariant T Cells, Driving Defective Metabolic and Functional Responses

Obesity underpins the development of numerous chronic diseases, such as type II diabetes mellitus. It is well established that obesity negatively alters immune cell frequencies and functions. Mucosal-associated invariant T (MAIT) cells are a population of innate T cells, which we have previously reported are dysregulated in obesity, with altered circulating and adipose tissue frequencies and a reduction in their IFN-g production, which is a critical effector function of MAIT cells in host defense. Hence, there is increased urgency to characterize the key molecular mechanisms that drive MAIT cell effector functions and to identify those which are impaired in the obesity setting. In this study, we found that MAIT cells significantly upregulate their rates of glycolysis upon activation in an mTORC1-dependent manner, and this is essential for MAIT cell IFN-g production. Furthermore, we show that mTORC1 activation is dependent on amino acid transport via SLC7A5. In obese patients, using RNA sequencing, Seahorse analysis, and a series of in vitro experiments, we demonstrate that MAIT cells isolated from obese adults display defective glycolytic metabolism, mTORC1 signaling, and SLC7A5 aa transport. Collectively, our data detail the intrinsic metabolic pathways controlling MAIT cell cytokine production and highlight mTORC1 as an important metabolic regulator that is impaired in obesity, leading to altered MAIT cell responses