Core fucosylation and its roles in gastrointestinal glycoimmunology

Glycosylation is a common post-translational modification in eukaryotic cells.It is involved in the production of many biologically active glycoproteins and the regulation of protein structure and function.Core fucosylation plays a vital role in the immune response.Most immune system molecules are core fucosylated glycoproteins such as complements,cluster differentiation antigens,immunoglobulins,cytokines,major histocompatibility complex molecules,adhesion molecules,and immune molecule synthesis-related transcription factors.These core fucosylated glycoproteins play important roles in antigen recognition and clearance,cell adhesion,lymphocyte activation,apoptosis,signal transduction,and endocytosis.Core fucosylation is dominated by fucosyltransferase 8(Fut8),which catalyzes the addition ofα-1,6-fucose to the innermost GlcNAc residue of N-glycans.Fut8 is involved in humoral,cellular,and mucosal immunity.Tumor immunology is associated with aberrant core fucosylation.Here,we summarize the roles and potential modulatory mechanisms of Fut8 in various immune processes of the gastrointestinal system.

Exercise immunology:Future directions

Several decades of research in the area of exercise immunology have shown that the immune system is highly responsive to acute and chronic exercise training.Moderate exercise bouts enhance immunosurveillance and when repeated over time mediate multiple health benefits.Most of the studies prior to 2010 relied on a few targeted outcomes related to immune function.During the past decade,technologic advances have created opportunities for a multi-omics and systems biology approach to exercise immunology.This article provides an overview of metabolomics,lipidomics,and proteomics as they pertain to exercise immunology,with a focus on immunometabolism.This review also summarizes how the composition and diversity of the gut microbiota can be influenced by exercise,with applications to human health and immunity.Exercise-induced improvements in immune function may play a critical role in countering immunosenescence and the development of chronic diseases,and emerging omics technologies will more clearly define the underlying mechanisms.This review summarizes what is currently known regarding a multi-omics approach to exercise immunology and provides future directions for investigators.

A Multi-Agent Immunology Model for Security Computer

This paper presents a computer immunology model for computer security, whose main components are defined as idea of Multi Agent. It introduces the natural immune system on the principle, discusses the idea and characteristics of Multi Agent. It gives a system model, and describes the structure and function of each agent. Also, the communication method between agents is described.

Immunology of tuberculosis

Various T cells and macrophages as well as cytokines are involved in the immunopathogenesis of tuberculosis(TB). A better understanding of immunology of TB can not only lead to the discovery of new immunodiagnostic tools, accelerate and facilitate the assessment of new therapeutic methods, but also find new treatment regimens. In this highlight topic we cover the latest developments in the role of T cells, macrophages, Natural killer(NK) cells, invariant NK T(iN KT) cells and γδ T cells with TB infection. Histologically, TB displays exudative inflammation, proliferative inflammation and productive inflammation depending on the time course. T cells first recognize antigen within the mycobacterially-infected lung, and then activate, differentiate, but the first T cell activation occurs in the draining lymph nodes of the lung. When protective T cells reach sufficient numbers, they can stop bacterial growth. Except for T cells, neutrophils also participate actively in defense against early-phase TB. NK cells are innate lymphocytes which are a first line of defense against mycobacterial infection. Human NK cells use the NKp46, NCRs and NKG2 D receptors to lyse Mycobacterium TB-infected monocytes and alveolar macrophages. NK cells produce not only interferon-γ, but also interleukin(IL)-22, which is induced by IL-15 and DAP-10. iN KT cells show different phenotypes and functions. Many iN KT cells are CD4+,few iN KT cells are CD8+, while an additional fraction of iN KT cells are negative for both CD4 and CD8. γδ T cells represent an early innate defense in antimycobacterial immunity. Studies done in humans and animal models have demonstrated complex patterns of γδ T cell immune responses during chronic TB. Human alveolar macrophages and monocytes can serve as antigen presentation cells for γδ T cells. Furthermore, the predominance of Vγ9Vδ2 T cells in TB has been confirmed.

Progresses in Integrated Traditional Chinese and Western Medical Research on Reproductive Immunology

Reproductive immunology is a crossed subject of reproductive biology and immunobiology. Great progresses have been achieved in the subject along with the deep development in life science. Modern reproductive immunology includes immunological regulation of fertility, materno-fetal immuno-regu-lation, and neuro-reproductive endocrino-immune network. With the integrated traditional Chinese and western medicine (ICWM) applied to reproductive immunology it has been greatly enriched in research contents and depth. The present review is to introduce the recent progresses in research of integrated medicine on reproductive immunology.

Old game, new players: Linking classical theories to new trends in transplant immunology

The evolutionary emergence of an efficient immune system has a fundamental role in our survival against pathogenic attacks. Nevertheless, this same protective mechanism may also establish a negative consequence in the setting of disorders such as autoimmunity and transplant rejection. In light of the latter, although research has long uncovered main concepts of allogeneic recognition, immune rejection is still the main obstacle to long-term graft survival. Therefore, in order to define effective therapies that prolong graft viability, it is essential that we understand the underlying mediators and mechanisms that participate in transplant rejection. This multifaceted process is characterized by diverse cellular and humoral participants with innate and adaptive functions that can determine the type of rejection or promote graft acceptance. Although a number of mediators of graft recognition have been described in traditional immunology, recent studies indicate that defining rigid roles for certain immune cells and factors may be more complicated than originally conceived. Current research has also targeted specific cells and drugs that regulate immune activation and induce tolerance. This review will give a broad view of the most recent understanding of the allogeneic inflammatory/tolerogenic response and current insights into cellular and drug therapies that modulate immune activation that may prove to be useful in the induction of tolerance in the clinical setting.

Systems Immunology Enabled Immune Engineering

The immune checkpoint blockade has revolutionized cancer treatment.However,not all cancer types are susceptible to this therapy.Even in melanoma,one of the best scenario,about half of the patients do not respond to immune checkpoint blockade.Since CD8+T cell is the main driving force behind cancer elimination,then having a complete and competent T cell repertoire to cover all possible cancer antigens expressed by cancer cells should be a determining factor to the success of this therapy.Conversely,if there are'holes'in patients’T cell repertoire and/or'weak spots'manifested as functional dysregulation or exhaustion on T cells specific to a set of cancer antigens that dominantly expressed by cancer cells,cancer immune escape is inevitable.However,these two types of cancer immune escape might need different treatment strategies:the first group with'holes'in the T cell repertoire,whether the'holes'are taking on a form of missing T cells to cover these cancer antigens or missing high-affinity TCRs that are known to be more sensitive to antigen stimulation,would be benefited from TCR re-directed adoptive cell transfer(ACT)therapy;the other group with T cell repertoire'weak spots'would be benefited from immune checkpoint blockade alone or in combination with additional stimulatory factors such as cytokines and peptide vaccine.In the past decade,we have developed several tools to profile the T cell repertoire from T cell receptor diversity to T cell receptor affinity to high-throughput linking antigen specificity to single T cell receptor sequences in large scale.In this talk,I will first introduce these tools and then give examples on how we use them to answer some of the fundamental questions in systems immunology with a focus on cancer immunology,which in turn help us design new therapeutics immune engineering.

尹玉新教授课题组在Nature Immunology发表研究成果

北京大学系统生物医学研究所尹玉新教授课题组最新研究发现了自身免疫系统调控开关——双重特异性磷酸酶2（dual-specificity phosphatase 2,DUSP2/PAC1）,它可以调控自身免疫反应,影响自身免疫疾病的发生发展,其相关研究论文＂The phosphatase DUSP2 controls the activity of the transcription activator STAT3 and regulates TH17 differentiation＂于2015年10月19日在线发表于Nature Immunology，北京大学基础医学院吕丹博士和2009级基础医学八年制博士研究生刘亮为该论文的共同第一作者。该项研究得到国家重点基础研究发展计划（973计划）、国家自然科学基金和北京大学一清华大学生命科学联合中心的支持。

Acknowledgments to reviewers of World Journal of Immunology

Many reviewers have contributed their expertise and time to the peer review,a critical process to ensure the quality of World Journal of Immunology.The editors and authors of the articles submitted to the journal are grateful to the following reviewers for evaluating the articles(including those published in this issue and those rejected for this issue)during the last editing time period.Azzam

Frontiers in Molecular Immunology

Immunology is a discipline to investigate the structure and function of the immune molecules or immune pathway and the causes of immunity to disease, which cover the study of all aspects of the immune system. The earliest concept of acquired immunology was originated from the inoculation of smallpox occurs inWan Quan’s (1499- 1582) Douzhenxinfa,[1] and was further developed by Edward Jenner with the discovery of smallpox vaccine in 1796.[2] Immunology made a great advance towards the end of the 19th century, with the isolation of infectious bacteria by Robert Koch[3] and the demonstration of antibody activity against diphtheria and tetanus toxins by Emil von Behring and Kitasato Shibasaburo.

International Conference on Immunology 2007

Shanghai,China July 12-15,2007 The conference will provide a forum to bring together immunologists and scientists from around the world in related fields to review the latest progress and development,to exchange their experience,progress

The sea bass Dicentrarchus labrax as a marine model species in immunology:Insights from basic and applied research

This review summarizes the current knowledge on immune defence activities of the European sea bass Dicentrarchus labrax by reporting the consistent amount of work done on this economically-important species.A draft genome sequence is available for this species,together with whole transcriptomes from lymphoid and non-lymphoid tissues.Available full-length coding sequences of many immunoregulatory and immune-related genes allow for targeted quantitative PCR analysis,nowadays needed for-omics data verification,ex vivo and in vitro.The first anti-T cells monoclonal antibody teleost-wise was obtained in sea bass,followed by several monoclonal and polyclonal markers of lymphocyte populations,namely T cells(pan-T,CD3ε,TcRγ,CD45),and B cells(IgM,IgT,IgD).The combined use of molecular and biochemical tools enabled investigations on innate and acquired immune responses of sea bass in unstimulated/stimulated fish,along the development and under variable environmental conditions and food regimes.An overview of sea bass viral and bacterial pathogens and available vaccines against these microorganisms is also provided.The knowledge accumulated in the past 25 years validates the European sea bass as a reference marine model in the field of fish immunology.

The implication of pyroptosis in cancer immunology:Current advances and prospects

Pyroptosis is a regulated cell death pathway involved in numerous human diseases,especially malignant tumors.Recent studies have identified multiple pyroptosis-associated signaling molecules,like caspases,gasdermin family and inflammasomes.In addition,increasing in vitro and in vivo studies have shown the significant linkage between pyroptosis and immune regulation of cancers.Pyroptosis-associated biomarkers regulate the infiltration of tumor immune cells,such as CD4^(+) and CD8^(+) T cells,thus strengthening the sensitivity to therapeutic strategies.In this review,we explained the relationship between pyroptosis and cancer immunology and focused on the significance of pyroptosis in immune regulation.We also proposed the future application of pyroptosis-associated biomarkers in basic research and clinical practices to address malignant behaviors.Exploration of the underlying mechanisms and biological functions of pyroptosis is critical for immune response and cancer immunotherapy.

New era of cancer immunology driven by big data

Cancer immunology has witnessed remarkable development over the past century.In the early 20^(th) century,William Coley embarked on pioneering efforts to activate the immune system against cancer using heat-killed Streptococcus pyogenes and Serratia marcescens^([1]).These attempts yielded varying clinical outcomes,some of which were notably successful,providing early evidence of the immune system’s potential in combating cancer.Moving into the mid-20th century,Dr.Lewis Thomas and Dr.Macfarlane Burnet introduced the concept“immune surveillance”^([2]).This theory proposed that the immune systemconstantlymonitors the body,identifying and eliminating emerging cancer cells to prevent them from developing into full-fledged tumors.This concept laid the foundation for future research in cancer immunology.Simultaneously,the concept of immune evasion emerged,emphasizing how cancer cells can elude immune detection and destruction,enabling them to proliferate and spread within the body.Thus,understanding and overcoming these mechanisms of immune escape became a pivotal focus of cancer immunotherapy.

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb titers.Methods:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 vaccine.All major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb serology.Results:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded exercise.However,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent manner.Both groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid antigens.nAbs increased significantly during exercise only in the hybrid immunity group.Conclusion:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

Synthetic immunology:T-cell engineering and adoptive immunotherapy

During the past decades,the rapidly-evolving cancer is hard to be thoroughly eliminated even though the radiotherapy and chemotherapy do exhibit efficacy in some degree.However,a breakthrough appeared when the adoptive cancer therapy[1]was developed,especially T cells armed with chimeric antigen receptors(CARs)showed great potential in tumor clinical trials recently.CAR-T cells successfully elevated the efficiency and specificity of cytotoxicity.In this review,we will talk about the design of CAR and CAR-included combinatory therapeutic applications in the principles of systems and synthetic immunology.

Liver immunology and its role in inflammation and homeostasis

The human liver is usually perceived as a non-immunological organ engaged primarily in metabolic, nutrient storage and detoxification activities. However, we now know that the healthy liver is also a site of complex immunological activity mediated by a diverse immune cell repertoire as well as non-hematopoietic cell populations. In the nondiseased liver, metabolic and tissue remodeling functions require elements of inflammation. This inflammation, in combination with regular exposure to dietary and microbial products, creates the potential for excessive immune activation. In this complex microenvironment, the hepatic immune system tolerates harmless molecules while at the same time remaining alert to possible infectious agents, malignant cells or tissue damage. Upon appropriate immune activation to challenge by pathogens or tissue damage, mechanisms to resolve inflammation are essential to maintain liver homeostasis. Failure to clear ＇dangerous＇ stimuli or regulate appropriately activated immune mechanisms leads to pathological inflammation and disrupted tissue homeostasis characterized by the progressive development of fibrosis, cirrhosis and eventual liver failure. Hepatic inflammatory mechanisms therefore have a spectrum of roles in the healthy adult liver; they are essential to maintain tissue and organ homeostasis and, when dysregulated, are key drivers of the liver pathology associated with chronic infection, autoimmunity and malignancy. In this review, we explore the changing perception of inflammation and inflammatory mediators in normal liver homeostasis and propose targeting of liver-specific immune regulation pathways as a therapeutic approach to treat liver disease.

Current research status of immunology in the genomic era

This review updates the current status of immunology research under the influence of genomics,both conceptually and technologically.It particularly highlights the advantages of employing the high-throughput and large-scale technology,the large genomic database,and bioinformatic power in the immunology research.The fast development in the fields of basic immunology,clinical immunology(tumor and infectious immunology) and vaccine designing is illustrated with respect to the successful usage of genomic strategy.We also speculate the future research directions of immunology in the era of genomics and post-genomics.

A Global Approach to Tumor Immunology

Biological and clinical advances in the understanding of tumor immunology suggest that immune responsiveness of human tumors is a complex biological phenomenon that could be best studied by a real-time comparison of tumor/host interactions in the tumor microenvironment through a high-throughput discovery-driven approach.This conclusion is derived from our recognition that too many hypotheses or,in other words,no solid single hypothesis exist,based on experimental results,to further drive experimentation in human subjects.Functional genomic studies entertained during the last few years consolidated the belief that in humans the interactions between tumor and immune cells are too complex to be approached exclusively with a hypothesis driven method.We believe that immune cells suit cancer cells in a Yin and Yang balance by opposing and yet mutually depending on each other.Indeed,immune infiltration in tumors may play a dual role modulating in different circumstances cancer cell growth or destruction through a physiological modulation of inflammation.It is reasonable to question what induces inflammation at the tumor site.We hypothesize that inflammation is primarily driven by the phenotype of tumor cells that can modulate their microenvironment through cell-to-cell interactions or the secretion of soluble factors.Thus,in analogy the observation of immune cells within tumors parallels the presence of paramedics,police and firemen at the scene of an accident,which is reactive to and not causative of the occurrence.In this review we will explore this hypothesis by reporting and summarizing most of our recent work in the frame of available literature on the subject.Cellular & Molecular Immunology.2004;1(4):256-265.