自噬的免疫调节作用和机制

Autophagy is a major pathway for degradation of cellular components and it contributes to the survival, differentiation, development, and dynamic homeostasis of organisms. Recent studies have demonstrated that autophagic mechanisms act as the effectors of immune systems, pattern recognition receptors and cy-tokines to clean the invasive pathogens in the cells. It was also found that immune systems recognize the invasive pathogens via monitoring the autophagic products. This pathway delivers the cytoplasmic material for lysosomal hydrolysis and presents the antigens to MHC Ⅱ molecules so as to activate the CD4 + T cells. Importantly, autophagy can couple with signaling for stress responses of cells and/or inflammatory responses to function as a defense. This paper reviewed the advance of rapidly developing research field and introduced the molecular mechanisms that autophagy regulates innate and adaptive immunity. These studies will deepen our understanding the mechanisms of immune responses and may provide a novel therapeutic strategy for autophage-associated diseases.     

自噬的免疫调节作用和机制

Autophagy is a major pathway for degradation of cellular components and it contributes to the survival, differentiation, development, and dynamic homeostasis of organisms. Recent studies have demonstrated that autophagic mechanisms act as the effectors of immune systems, pattern recognition receptors and cy-tokines to clean the invasive pathogens in the cells. It was also found that immune systems recognize the invasive pathogens via monitoring the autophagic products. This pathway delivers the cytoplasmic material for lysosomal hydrolysis and presents the antigens to MHC Ⅱ molecules so as to activate the CD4 + T cells. Importantly, autophagy can couple with signaling for stress responses of cells and/or inflammatory responses to function as a defense. This paper reviewed the advance of rapidly developing research field and introduced the molecular mechanisms that autophagy regulates innate and adaptive immunity. These studies will deepen our understanding the mechanisms of immune responses and may provide a novel therapeutic strategy for autophage-associated diseases.     

Direct and indirect role of Toll-like receptors in T cell mediated immunity

Toll-like receptors (TLR) are pathogen-associated molecular patterns (PAMPs) recognition receptors that playan important role in protective immunity against infection and inflammation.They act as central integrators ofa wide variety of signals,responding to diverse agonists of microbial products.Stimulation of Toll-like receptorsby microbial products leads to signaling pathways that activate not only innate,but also adaptive immunity byAPC dependent or independent mechanisms.Recent evidence revealed that TLR signals played a determiningrole in the skewing of na(?)ve T cells towards either Th1 or Th2 responses.Activation of Toll-like receptors alsodirectly or indirectly influences regulatory T cell functions.Therefore,TLRs are required in both immuneactivation and immune regulation.Study of TLRs has significantly enhanced our understanding of innate andadaptive immune responses and provides novel therapeutic approaches against infectious and inflammatorydiseases.Cellular & Molecular Immunology.2004;1(4):239-246.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

锌指蛋白A20对Toll样受体信号途径的负反馈调控及其对机体的保护作用

Toll-like receptors (TLRs) recognize pathogens and initiate innate immune responses at the early stage of virus invasion, promoting the maturation and differentiation of immune cells, regulating immune respon-ses,and triggering inflammatory responses. Lipopolysaccharide (LPS) activates the TLR4 signaling pathways which result in the activation of NFκB and JNK/SAPK and the expression of large amounts of inflammatory fac-tors,leading to systemic inflammatory response and multiple organ failure. A20, a NFκB-dependant cytosolic protein, via a negative feedback loop blocks NFκB activation and participates in the regulation of inflammatory responses and the inhibition of apptosis;therefore, it provides protective effect on the body.     

The ubiquitin-proteasome system and its role in inflammatory and autoimmune diseases

Protein degradation through the ubiquitin-proteasome system is the major pathway of non-lysosomal proteolysis of intracellular proteins. It plays important roles in a variety of fundamental cellular processes such as regulation of cell cycle progression, division, development and differentiation, apoptosis, cell trafficking, and modulation of the immune and inflammatory responses. The central element of this system is the covalent linkage of ubiquitin to targeted proteins, which are then recognized by the 26S proteasome, an adenosine triphosphate-dependent, multi-catalytic protease. Damaged, oxidized, or misfolded proteins as well as regulatory proteins that control many critical cellular functions are among the targets of this degradation process. Aberration of this system leads to the dysregulation of cellular homeostasis and the development of multiple diseases. In this review, we described the basic biochemistry and molecular biology of the ubiquitin-proteasome system, and its complex role in the development of inflammatory and autoimmune diseases. In addition, therapies and potential therapeutic targets related to the ubiquitin-proteasome system are discussed as well.