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.     

Intercellular trogocytosis plays an important role in modulation of immune responses

Intercellular communication is an important means of molecular information transfer through exchange of membrane proteins from cells to cells. Advent of the latest analytical and imaging tools has allowed us to enhance our understanding of the cellular communication through the intercellular exchange of intact membrane patches, also called trogocytosis, which is a ubiquitous phenomenon. Immune responses against pathogens or any foreign antigens require fine immune regulation, where cellular communications are mediated by either soluble or cell surface molecules. It has been demonstrated that the membrane molecule transfer between immune cells such as dendritic and T cells can be derived through internalization/recycling pathway, dissociation-associated pathway, uptake of exosomes and membrane nanotube formations. Recent evidence implicates the trogocytosis as an important mechanism of the immune system to modulate immune responses. Exchange of membrane molecules/ antigens between immune cells has been observed for a long time, but the mechanisms and functional consequences of these transfers remain unclear. In this review, we discuss the possible mechanisms of trogocytosis and its physiological relevance to immune system, with special reference to T cells and the stimulatory or suppressive immune responses derived from T cells with acquired dendritic cell membrane molecules. Cellular ＆ Molecular Immunology. 2008;5（4）：261-269.     

CD52 as both a marker and an effector molecule of T cells with regulatory action： Identification of novel regulatory T cells

Regulation of immune responses is central to an effective clearance of pathogens. An effective immune response is also necessary for preventing the development of cancer and auto- immune diseases and for maintaining homeostasis. Although the thymus is the central lymphoid organ that regulates immune responses for self-tol- erance during the maturation of T cells, regulatory immune cells are still required for the proper functioning of mature immune cells in the periphery. Regulatory cells are a subpopulation of immune cells that suppress proliferation and cytokine production by other immune cells in res- ponse to antigenic stimulation.     

Modulation of Neuroimmune Responses on Glia in the Central Nervous System： Implication in Therapeutic Intervention against Neuroinflammation

It has long been known that the brain is an immunologically privileged site in normal conditions. Although the cascade of immune responses can occur as long as there is a neuronal injury or a potent immune stimulation, how the brain keeps glial cells in a quiescent state is still unclear. Increasing efforts have been made by several laboratories to elucidate how repression oi~ immune responses is achieved in the neuronal environment. The suppression factors include neurotransmitters, neurohormones, neurotrophic factors, anti-inflammatory factors, and cell-cell contact via adhesion molecules or CD200 receptor. This review discusses how these factors affect the cascade of cerebral immune responses because no single factor listed above can fully account for the immune suppression. While several factors contribute to the suppression of immune responses, activation of glial cells and their production of pro-inflammatory factors do occur as long as there is a neuronal injury, suggesting that some neuronal components facilitate immune responses. This review also discusses which signals initiate or augment cerebral immune responses so that stimulatory signals override the suppressive signals. Increasing lines of evidence have demonstrated that immune responses in the brain are not always detrimental to neurons. Attempt to simply clear off inflammatory factors in the CNS may not be appropriate for neurons in neurological disorders. Appropriate control of immune cells in the CNS may be beneficial to neurons or even neuroregeneration. Therefore, understanding the mechanisms underlying immune suppression may help us to reshape pharmacological interventions against inflammation in many neurological disorders.     

Salmonella Typhi： from a Human Pathogen to a Vaccine Vector

Salmonella （S.） typhi is an important intracellular pathogen. Among the more than 2,300 closely-related Salmonella serovars bacteria recognized, S. typhi is the only one that is pathogenic exclusively for humans, in whom it causes typhoid or enteric fever. The pathogen has been around for many years and many studies have been done in an effort to combat it. Molecular and biologic features of S. typhi and host factors and immune responses involved in Salmonella invasion have been extensively studies. Vaccines that have been developed most notably are Vi polysaccharide and Ty21a. However, as the results show, there is still a long way to go. It is also shown that multi-drug resistance has occurred to the few available antibiotics. More and more studies have shown that Salmonella can be used as a vaccine vector carrying antigens of other pathogens. This has been promising in that the immune system can be elicited in response to both the Salmonella bacteria and the antigen of the pathogen in question. This review aims to highlight some of the milestones attained in the fight against the disease from the time S. typhi was seen as a pathogen causing typhoid fever to the use of Salmonella as a vaccine vector. Cellular ＆ Molecular Immunology.     

Dendritic cells as a pharmacological target of traditional Chinese medicine

Dendritic cells （DCs） represent a heterogeneous population of professional antigen-presenting cells （APCs） that play a central role in the initiation and regulation of immune responses. There is considerable evidence that DCs can be used as therapeutic targets for pharmacological modulation of immune responses. Traditional Chinese medicine （TCM） has a long-standing history of using herbal medicine in the treatment of variety of human diseases. Many of the clinical effects of TCM have reportedly been attributed to the up- or down-regulation of immune responses. Accumulating evidence indicates that TCM and its components can interfere with immune responses at the earliest stage by targeting key functions of DCs. Here, we review those published studies of TCM with respect to their effects on immunobiological functions of DCs. Investigations based on both chemical entities derived from TCM as well as TCM herbal mixtures are presented. These studies suggest that various TCM herbal medicines have the capacity to inhibit or promote major functions of DCs, such as differentiation, maturation, cytokine production, survival, antigen uptake and presentation as well as trafficking. These studies have revealed novel biological effects of TCM and documented the utility of this approach to discover novel biological modifier of DC functions derived from natural sources.     

Act1作用的分子机制及其与免疫损伤性疾病关系的研究进展

T and B cell-mediated immune responses play a critical role in the control and modulation of autoimmune diseases. NF-kappa B Activator 1 (Act1) , also called (connection to Iκ B kinase and stress-activated protein kinases,CIKS), is a recently identified molecule, which activates NF-κB . Recent studies have shown that Act1 is a key positive regulator of IL-17 signaling pathway ,and an important negative regulator of B cell-mediated humeral immune responses through its function in CD40L and BAFF signaling. Act1 is critical for TH17 and B cell mediated autoimmune and inflammatory responses. Moreover, Actl may play important roles in ontogenesis. Such seemingly opposite functions of Act1 in CD40-BAFFR and IL-17R signaling are orchestrated by different domains in Act1. Such delicate regulatory mechanisms may provide a common vehicle to promote balance between host defense to pathogens and tolerance to self.     

Dendritic cells in cancer immunology

The clinical success of immune checkpoint therapy(ICT)has produced explosive growth in tumor immunology research because ICT was discovered through basic studies of immune regulation.Much of the current translational efforts are aimed at enhancing ICT by identifying therapeutic targets that synergize with CTLA4 or PD1/PD-L1 blockade and are solidly developed on the basis of currently accepted principles.Expanding these principles through continuous basic research may help broaden translational efforts.With this mindset,we focused this review on three threads of basic research directly relating to mechanisms underlying ICT.Specifically,this review covers three aspects of dendritic cell(DC)biology connected with antitumor immune responses but are not specifically oriented toward therapeutic use.First,we review recent advances in the development of the cDC1 subset of DCs,identifying important features distinguishing these cells from other types of DCs.Second,we review the antigen-processing pathway called cross-presentation,which was discovered in the mid-1970s and remains an enigma.This pathway serves an essential in vivo function unique to cDC1s and may be both a physiologic bottleneck and therapeutic target.Finally,we review the longstanding field of helper cells and the related area of DC licensing,in which CD4 T cells influence the strength or quality of CD8 T cell responses.Each topic is connected with ICT in some manner but is also a fundamental aspect of cell-mediated immunity directed toward intracellular pathogens.     

Selective Function of PKC-θ in T cells

T cell activation is a critical process in initiating adaptive immune response since only through this process the naive antigen specific T cells differentiate into armed effector T cells that mediate the actual immune response. During T cell activation, naive T cells undergo clonal expansion and acquire the capability to kill target cells infected with pathogens or produce cytokines essential for regulating immune response. Inappropriate activation or inactivation of T cells leads to autoimmunity or severe immunodeficiencies. PKC-θ is selectively expressed in T cells and required for mediating T cell activation process. Mice deficient in PKC-θ exhibit defects in T cell activation, survival and activation-induced cell death. PKC-θ selectively translocates to immunological synapse and mediates the signals required for activation of NF-κB, AP1 and NFAT that are essential for T cell activation. Furthermore, PKC-θ^-│- mice displayed multiple defects in the development of T cell-mediated immune responses in vivo. PKC-θ is thus a critical molecule that regulates T cell function at multiple stages in T cell-mediated immune responses in vivo.     

Expression and purification of soluble human programmed death-1 in Escherichia coli

Programmed death-1 （PD-1）, a member of CD28 family, is able to negatively regulate the TCR complex-initiated signaling by interacting with its cognate ligands （PD-L1 and/or PD-L2）. PD-1/PD-L1 pathway plays an important role in down-regulating the effective phase of adaptive immune responses and the blockade of this pathway has been proved to enhance antiviral and antitumoral immunity, suggesting that it might be a potential target for the development of therapies to improve T cell responses in patients with virus infections or malignancies. In present study, the extracellular domain of human PD-1 with a carboxyl terminal His-tag （designated as sPD-1） was expressed as inclusion bodies in Escherichia coll. The product was on-column refolded, purified by immobilized metal affinity chromatography, and characterized by Western blotting. Furthermore, the soluble PD-1 with high purity possessed specific binding activity with its cognate ligand PD-L1, and the dissociation constant was 0.43 nmol/L as determined by Scatchard plot analysis. These results suggest that refolded sPD-1 from prokaryotic cells may be of therapeutic interest in enhancing antivirus and antitumoral immune responses.