Autophagy–physiology and pathophysiology

“Autophagy” is a highly conserved pathway for degradation, by which wasted intracellular macromolecules are delivered to lysosomes, where they are degraded into biologically active monomers such as amino acids that are subsequently re-used to maintain cellular metabolic turnover and homeostasis. Recent genetic studies have shown that mice lacking an autophagy-related gene (Atg5 or Atg7) cannot survive longer than 12 h after birth because of nutrient shortage. Moreover, tissue-specific impairment of autophagy in central nervous system tissue causes massive loss of neurons, resulting in neurodegeneration, while impaired autophagy in liver tissue causes accumulation of wasted organelles, leading to hepatomegaly. Although autophagy generally prevents cell death, our recent study using conditional Atg7-deficient mice in CNS tissue has demonstrated the presence of autophagic neuron death in the hippocampus after neonatal hypoxic/ischemic brain injury. Thus, recent genetic studies have shown that autophagy is involved in various cellular functions. In this review, we introduce physiological and pathophysiological roles of autophagy

Cross-talk between cd1d-restricted nkt cells and γδ cells in t regulatory cell response

CD1d is a non-classical major histocompatibility class 1-like molecule which primarily presents either microbial or endogenous glycolipid antigens to T cells involved in innate immunity. Natural killer T (NKT) cells and a subpopulation of γδ T cells expressing the Vγ4 T cell receptor (TCR) recognize CD1d. NKT and Vγ4 T cells function in the innate immune response via rapid activation subsequent to infection and secrete large quantities of cytokines that both help control infection and modulate the developing adaptive immune response. T regulatory cells represent one cell population impacted by both NKT and Vγ4 T cells. This review discusses the evidence that NKT cells promote T regulatory cell activation both through direct interaction of NKT cell and dendritic cells and through NKT cell secretion of large amounts of TGFβ, IL-10 and IL-2. Recent studies have shown that CD1d-restricted Vγ4 T cells, in contrast to NKT cells, selectively kill T regulatory cells through a caspase-dependent mechanism. Vγ4 T cell elimination of the T regulatory cell population allows activation of autoimmune CD8+ effector cells leading to severe cardiac injury in a coxsackievirus B3 (CVB3) myocarditis model in mice. CD1d-restricted immunity can therefore lead to either immunosuppression or autoimmunity depending upon the type of innate effector dominating during the infection

Prenatal and postnatal exposure to perfluoroalkyl substances and antibody concentrations with mass vaccination in 5, 8, 11 and 14 year-old children in Taiwan

[[abstract]]RATIONALE: Perfluoroalkyl substances (PFASs) are wide spread persistant compounds which have half-life of 3-15 years in human bodies. PHASs have been found associated with decreased toxoid antibody concentrations, and increased atopy risk in children. We aim to examine the association between PFASs exposure and children antibody levels. METHODS: We utilized a birth cohort established in 2000-2001 consisting 610 pregnant women and their children followed at 2, 5, 8, 11, and 14 years old. Due to lost-to follow-up and lake of sufficient serum, 376 and 69 children have PFASs quantified at birth and 8-year old, respectively. Antibody concentrations were analyzed for 90, 104, 69 and 92 children at 5, 8, 11, and 14 years, respectively. The last time mass vaccination was during 5-6 year-old in Taiwan. Co-exposure of phthalate, inorganic arsenic, chromium and cadmium was considered. RESULTS: PFOS and PFOA levels were generally slightly lower but PFNA was higher than in the US and northern Europe. High correlation and comparable PFASs and antibody concentrations between maternal and cord blood was established, apart from that cord blood had much higher PFHxS than maternal venous blood (median, 22.8 vs. 1.0 ng/mL). Preliminary results showed cord blood PFASs appear to associate with decreased antibody against tetanus, rubella and HBV. For example cord blood PFDoA was correlated with decreased tetanus antibody concentrations at 5 and 14 years, with r 5 -0.31 (p < 0.01) and -0.37 (p < 0.001), respectively. CONCLUSIONS: Clinical management concerning re-booster of certain vaccinations may have PHASs exposure considered because children immune Th1/Th2 might be unbalanced. Further mechanistic study is warranted