Aureane-type sesquiterpene tetraketides as a novel class of immunomodulators with interleukin-17A inhibitory activity

Interleukin(IL)-17A,a pro-inflammatory cytokine,is a fundamental function in the onset and advancement of multiple immune diseases.To uncover the primary compounds with IL-17A inhibitory activity,a large-scale screening of the library of traditional Chinese medicine constituents and microbial secondary metabolites was conducted using splenic cells from IL-17A-GFP reporter mice cultured under Th17-priming conditions.Our results indicated that some aureane-type sesquiterpene tetraketides isolated from a wetland mud-derived fungus,Myrothecium gramineum,showed remarkable IL-17A inhibitory activity.Nine new aureane-type sesquiterpene tetraketides,myrogramins A-I(1,4-11),and two known ones(2 and 3)were isolated and identified from the strain.Compounds 1,3,4,10,and 11 exhibited significant IL-17A inhibitory activity.Among them,compound 3,with a high fermentation yield dosedependently inhibited the generation of IL-17A and suppressed glycolysis in splenic cells under Th17-priming conditions.Strikingly,compound 3 suppressed immunopathology in both IL-17A-mediated animal models of experimental autoimmune encephalomyelitis and pulmonary hypertension.Our results revealed that aureane-type sesquiterpene tetraketides are a novel class of immunomodulators with IL-17A inhibitory activity,and hold great promise applications in treating IL-17A-mediated immune diseases.

Metabolic Control ofγδT Cell Function

Metabolic change is associated with cell activities,such as signal transduction,cell differentiation,and cell cycle.In the pathogenesis of autoimmune diseases,abnormal activation of T cells is often accompanied by changes in their metabolism.Conversely,the changes of metabolites can also regulate the proliferation,differentiation,and function of T cells.As a bridge between innate and adaptive immune responses,γδT cells have unique biological characteristics and functions.However,the immunometabolic mechanism ofγδT cells has been a novel field for research in recent years.In this review,we summarize the influence of metabolic pathways and nutrients onγδT cell function,and metabolic features ofγδT cell subsets,which may provide new insights in interventions targetingγδT cells in disease control.

Gut microbiota have blood types as human

ABO blood group system was firstly recognized by Landsteiner in 1900[1].Since then,the antigens of the ABO system (A,B and H determinants,respectively)have been shown to encompass complex carbohydrate structures [2].A and B antigen were synthesized by the sequential action of glycosyltransferases,with A and B glycosyltransferases catalyzing the addition of N-acetylgalactosamine and D-galactose to precursor H antigen,respectively. Group O individuals lack such transferase enzymes and consequently continue to express the basic H structure only [3,4].It is determined that approximate 2million ABH glycan antigen sites are presented on each red blood cell [5].Additionally,the ABH antigens are widely expressed in other human ceils and tissues,including the sensory neurons,epithelium,the vascular endothelium and platelets [6].