M2-specific reduction of CD1d switches NKT cell-mediated immune responses and triggers metaflammation in adipose tissue

Metaflammation is responsible for several metabolic syndromes,such as type 2 diabetes.However,the mechanisms by which metabolic disorders trigger metaflammation remain unclear.We identified a cell type-specific downregulation of CD1d expression in M2 macrophages during the progression of obesity prior to the onset of inflammation in visceral adipose tissues.A reduction in CD1d expression influenced the ability of M2 macrophages to present antigens and caused a change in antigen-presenting cells from M2 macrophages to M1 macrophages.With CD1d conditional knockout(KO)mice,we further demonstrated that natural killer T(NKT)cell activation by M2 macrophages inhibited metaflammation and insulin resistance by promoting Th2 responses and M2 polarization in visceral adipose tissues of obese mice,whereas NKT cell activation by M1 macrophages exacerbated metaflammation and insulin resistance by promoting Th1 responses and inhibiting M2 polarization.Our results suggest that an M2-specific reduction of CD1d is an initiating event that switches NKT cell-mediated immune responses and disrupts the immune balance in visceral adipose tissues in obese mice.

Dietary habits, lifestyle factors and neurodegenerative diseases

Worldwide stroke is increasing in parallel with modernization,changes in lifestyle,and the growing elderly population.Our review is focused on the link between diet,as part of‘modern lifestyle’,and health in the context of genetic predisposition of individuals to‘unhealthy’metabolic pathway activity.It is concluded that lifestyle including high sugar diets,alcohol and tobacco addiction or high fat diets as well as ageing,brain injury,oxidative stress and neuroinflammation,negatively influence the onset,severity and duration of neurodegenerative diseases.Fortunately,there are several healthy dietary components such as polyunsaturated fatty acids and the anti-oxidants curcumin,resveratrol,blueberry polyphenols,sulphoraphane,salvionic acid as well as caloric restriction and physical activity,which may counteract ageing and associated neurodegenerative diseases via increased autophagy or increased neurogenesis in the adult brain.

Dysregulation of circular RNAs in inflammation and cancers

Emerging lines of evidence have shown that the production of the covalently closed single-stranded circular RNAs is not splicing errors,but rather a regulated process with distinct biogenesis and turnover.Circular RNAs are expressed in a cell type-and tissue-specific manner and often localize to specific subcellular regions or organelles for functions.The dysregulation of circular RNAs from birth to death is linked to the pathogenesis and progression of diverse diseases.This review outlines how aberrant circular RNA biogenesis,subcellular location,and degradation are linked to disease progression,focusing on metaflammation and cancers.We also discuss potential therapeutic strategies and obstacles in targeting such disease-related circular RNAs.