Apoptotic cell capture by DCs induces unexpectedly robust autologous CD4+ T‐cell responses

Apoptotic cells represent an important source of self‐antigens and their engulfment by dendritic cells (DCs) is usually considered to be related to tolerance induction. We report here an unexpectedly high level of human CD4⁺ T‐cell proliferation induced by autologous DCs loaded with autologous apoptotic cells, due to the activation of more than 10% of naive CD4⁺ T cells. This proliferation is not due to an increase in the costimulatory capacity of DCs, but is dependent on apoptotic cell‐associated material processed through an endo‐lysosomal pathway and presented on DC MHC class II molecules. Autologous CD4⁺ T cells stimulated with apoptotic cell‐loaded DCs exhibit suppressive capacities. However, in the presence of bacterial lipopolysaccharide, apoptotic cell‐loaded DCs induce the generation of IL‐17‐producing cells. Thus, apoptotic cell engulfment by DCs may lead to increased autologous responses, initially generating CD4⁺ T cells with suppressive capacities able to differentiate into Th17 cells in the presence of a bacterial danger signal such as LPS.     

Putative association between the -1415 T/C polymorphism of spermidine/spermine N1-acetyltransferase (SSAT1) gene and alcohol use disorders in women and men

Background: The activity of N-methyl-D-aspartate (NMDA) glutamate receptor, which responds to the levels of polyamines, modifies the neurotoxicity caused by ethanol. We aimed to investigate if the functionality of the spermidine/spermine N1-acetyltransferase (SSAT1) gene could be associated with a differential risk for alcoholism. Methods: We studied a sample of 586 subjects: 104 alcohol-dependent patients, 273 patients with psychiatric disorders but without substance dependence, and 209 healthy controls. After gender stratification, the allele frequency distribution of the SSAT1 gene was compared between these three groups. Results: In females, the TC genotype was significantly more frequent in alcohol-dependent patients than in non-alcohol-dependent psychiatric controls (χ^2?=?7.509 df?=?2, p?=?0.023). A trend was found when alcohol-dependent females were compared with the healthy control group (χ^2?=?4.897 df?=?2, p?=?0.086). No statistical differences were found among the males. Discussion and conclusion: Gender differences in the regulation of SSAT1 gene expression may possibly be due to gender-specific effects of stress, ethanol toxicity, and/or polyamines levels. Further studies are needed to confirm our findings.     

Carbohydrate supplementation increases intramyocellular lipid stores in elite runners

The objective was to determine the effects of carbohydrate (CHO) supplementation on exercise-induced hormone responses and post-training intramyocellular lipid stores (IMCL). Twenty-four elite male athletes (28.0 ± 1.2 years) were randomized to receive CHO (maltodextrin solution) or zero energy placebo solution (control group). The high-intensity running protocol consisted of 10 × 800 m at 100% of the best 3000-m speed (Vm3 km) and 2 × 1000 m maximal bouts in the morning and a submaximal 10-km continuous easy running in the afternoon of day 9. IMCL concentrations were assessed by ¹H-MRS before (?day 9) and after training (day 9) in soleus (SO) and tibialis anterior (TA) muscles. Blood hormones were also measured before, during, and post-exercise. The percent change (Δ%) in TA-IMCL was higher in the CHO group (47.9 ± 24.5 IMCL/Cr) than in the control group (?1.7 ± 13.1, respectively) (P = .04). Insulin concentrations were higher in the CHO group post-intermittent running compared to control (P = .02). Circulating levels of free fatty acids and GH were lower in the CHO group (P > .01). The decline in performance in the 2nd 1000-m bout was also attenuated in this group compared to control (P < .001 and P = .0035, respectively). The hormonal milieu (higher insulin and lower GH levels) in the CHO group, together with unchanged free fatty acid levels, probably contributed to the increased IMCL stores. This greater energy storage capacity may have improved post-exercise recovery and thus prevented performance deterioration.