Background/Aims: Despite strong association between obesity and the pathogenesis of type 2 diabetes (T2D), only a subset of obese individuals eventually develops T2D. We sought to determine the immunological factors behind this heterogeneity. Methods: Peripheral blood of obese non-diabetic subjects and obese diabetic subjects were collected and the B cell responses in these subjects were analyzed. Results: We found that the B cells from obese diabetic subjects had similar B cell subtype composition and secreted similar levels of low-grade pro-inflammatory cytokines to obese non-diabetic subjects, characteristic to the background chronic immune activation frequently observed in obese subjects. When examining adaptive B cell antibody responses, however, obese diabetic subjects presented much higher levels of polyclonal activation and antibody secretion, with impaired ability to response to new antigens such as seasonal influenza vaccination. Conclusions: These data demonstrated that in obese diabetic subjects, B cell adaptive response is impaired and potentially contribute to overall higher inflammation.

Non-alcoholic fatty liver disease (NAFLD) comprises a range of liver diseases, between steatosis and non‑alcoholic steatohepatitis and liver cirrhosis, which are closely associated with diabetes mellitus. Previous studies have indicated that oxidative stress is a key factor in the development of NAFLD. Molecular hydrogen (H2) may ameliorate oxidative stress injuries by selectively neutralizing peroxynitrite and hydroxyl radicals. The present study evaluated the effects of H2 on NAFLD in rats and concluded that H2‑rich saline had significant therapeutic effects on NAFLD induced by hyperglycemia and hyperlipidemia, as demonstrated by hematoxylin and eosin and terminal deoxynucleotidyl-transferase‑mediated dUTP nick end labeling staining. H2‑rich saline improved fasting blood glucose, fasting insulin, insulin sensitivity and glucose tolerance, and lowered the expression levels of tumor necrosis factor alpha, interleukin‑1 beta, 3‑nitrotyrosine and 8‑hydroxy‑2'‑deoxyguanosine in the liver. In addition, the present study revealed that H2‑rich saline could significantly increase peroxisome proliferator‑activated receptor (PPAR) α and PPARγ expression in hepatocytes. In conclusion, H2‑rich saline may significantly improve NAFLD, possibly by reducing oxidative stress and activating hepatic PPARα and PPARγ expression.

Type 2 diabetes mellitus (T2DM) is characterized by a chronic low-grade inflammatory state. Follicular helper T cells (Tfh) play critical roles in inducing B-cell activation and producing various cytokines, whereas circulating CD4+CXCR5+ T cells (CTfh) may act as a counterpart to measure Tfh cell disorders. In this study, we investigated whether Tfh could be involved in the development of T2DM by assessing CTfh in peripheral blood. CTfh and it subtypes were determined by measuring CD3, CD4, CXCR5, CXCR3, and CCR6 in 68 T2DM patients and 60 healthy controls using flow cytometry. Results showed that proportion of CTfh in the peripheral CD4+ T cells was significantly increased in T2DM patients (8.5 ± 0.5%) than in controls (4.5 ± 0.3%) (p < 0.001). Further study revealed that the balance of CTfh subtypes was greatly dysregulated, in which percentage of Th17 subtype was significantly increased in patients. Investigating the correlation between CTfh and risk factors of T2DM demonstrated that proportion of CTfh were significantly elevated in patients with body mass index (BMI) over 24.0 (p = 0.005). Interestingly, patients with abdominal obesity had further increase in CTfh than those without abdominal obesity. This study suggests the involvement of CTfh in T2DM, especially in T2DM-related obesity.

The aim of this study was to investigate the immunomodulatory effects and mechanism of action of alpha-melanocytestimulating hormone (a-MSH) gene modified proteolipid protein (PLP) 139-151-specific T cells (T PLP-a-MSH ) in the SJL mouse model of experimental autoimmune encephalomyelitis (EAE). PLP139-151-specific T cells (T PLP cells) were transduced with a recombinant adeno-associated virus 2 (rAAV2) encoding a-MSH. After activation with PLP139-151 in vitro, T PLP-a-MSH cells secreted high levels of a-MSH and also demonstrated an altered Th1-like cytokine pattern as well as a high frequency of CD4 + CD25 + Treg cells. Transfer studies showed that T PLP-a-MSH cells could suppress the induction of adoptive transfer EAE. More importantly, our studies demonstrated that T PLP-a-MSH cells had preventive and therapeutic effect on active relapse-remitting EAE (REAE) in an antigen-inducible manner. Suppression of REAE by T PLP-a-MSH cells was associated with a general reduction of inflammatory central nervous system (CNS) infiltrates, a pronounced decrease in Th1 cytokines and chemokines expression and an increase in Th2 cytokines. These data strongly suggested that local delivery of a-MSH by rAAV2-mediated a-MSH-transduced PLP139-151-specific T cells (T PLP-a-MSH ) would be a desirable new approach to the treatment of autoimmune disease in the CNS.

The concept of "controlled oxygenated rewarming" (COR) using ex vivo machine perfusion after cold storage was evaluated as tool to improve renal graft function after transplantation. Renal function after 20 min warm ischemia and 21 h cold storage was studied in an auto-transplant model in pigs (25-30 kg, n = 6 per group). In the study group, preimplant ex vivo machine perfusion for 90 min was added after cold storage, including gentle warming up of the graft to 20°C (COR). Kidneys that were only cold stored for 21 h served as controls. In vivo follow up was one week; the remaining native kidney was removed during transplantation. COR significantly improved cortical microcirculation upon early reperfusion and reduced free radical mediated injury and cellular apoptosis. Post-transplant kidney function (peak levels in serum) was also largely and significantly improved in comparison to the control group. A weak inverse correlation was found between renal flow during COR and later peak creatinine after transplantation (r = 0.5), better values were seen for oxygen consumption, measured during machine perfusion at 20°C (r = 0.81). Gentle graft rewarming prior to transplantation by COR improves post-transplant graft outcome and may also be a valuable adjunct in pretransplant graft assessment.