International Reviews of Immunology最新文献

Worldwide COVID-19 pandemic has taken a huge toll of morbidity and mortality. In selected patients, classified as severe, the overwhelming inflammatory state imposed by this infection is accompanied by a hypercoagulable state, hallmarked by a unique pattern; a marked increase in D-dimer, out of proportion to other markers of coagulopathy. In this review, we turn a spotlight to this phenomenon, offering a unified conceptual model depicting the leading hypotheses of coagulopathy in COVID-19. The key players of the coagulation cascades accompanying the COVID-19 inflammation malfunction on virtually every level; tissue factor expression is amplified, physiological anti-coagulant pathways (anti-thrombin, protein C and S, and the inhibitor of the tissue factor pathway) are impaired and fibrinolysis is inhibited. Components of autoimmunity, the complement system amongst others, further contribute to the pathology. As data continue to gather, our model offers a pathophysiological overview of COVID-19 coagulopathy, defined by the resultant histopathology: either intra-vascular or extra-vascular. We hope this review will facilitate understanding and serve as a lead point to future therapeutic directives.

An increasing number of researches have shown that cell metabolism regulates cell function. Dendritic cells (DCs), a professional antigen presenting cells, connect innate and adaptive immune responses. The preference of DCs for sugar or lipid affects its phenotypes and functions. In many diseases such as atherosclerosis (AS), diabetes mellitus and tumor, altered glucose or lipid level in microenvironment makes DCs exert ineffective or opposite immune roles, which accelerates the development of these diseases. In this article, we review the metabolism pathways of glucose and cholesterol in DCs, and the effects of metabolic changes on the phenotype and function of DCs. In addition, we discuss the effects of changes in glucose and lipid levels on DCs in the context of different diseases for better understanding the relationship between DCs and diseases. The immune metabolism of DCs may be a potential intervention link to treat metabolic-related immune diseases.

Spleen tyrosine kinase (Syk) is a cytoplasmic non-receptor protein tyrosine kinase expressed in a variety of cells and play crucial roles in signal transduction. Syk mediates downstream signaling by recruiting to the dually phosphorylated immunoreceptor tyrosine-based activation motifs (ITAMs) of the transmembrane adaptor molecule or the receptor chain itself. In gut diseases, Syk is observed to be expressed in intestinal epithelial cells, monocytes/macrophages, dendritic cells and mast cells. Activation of Syk in these cells can modulate intestinal mucosal immune response by promoting inflammatory cytokines and chemokines production, thus regulating gut homeostasis. Due to the restriction of specificity and selectivity for the development of Syk inhibitors, only a few such inhibitors are available in gut diseases, including intestinal ischemia/reperfusion damage, infectious disease, inflammatory bowel disease, etc. The promising outcomes of Syk inhibitors from both preclinical and clinical studies have shown to attenuate the progression of gut diseases thereby indicating a great potential in the development of Syk targeted therapy for treatment of gut diseases. This review depicts the characterization of Syk, summarizes the signal pathways of Syk, and discusses its potential targeted therapy for gut diseases.

Many recent studies have reported the onset of a robust antibody response to SARS-CoV-2 infection and highlighted produced antibodies' specific qualitative and quantitative aspects, relevant for developing antibody-based diagnostic and therapeutic options. In this review, firstly we will report main information acquired so far regarding the humoral response to COVID-19; we will concentrate, in particular, upon the observed levels and the kinetics, the specificity spectrum and the neutralizing potential of antibodies produced in infected patients. We will then discuss the implication of humoral response's characteristics in the development and correct use of serologic tests, as well as the efficacy and safety of convalescent plasma therapy and of neutralizing monoclonal antibodies for treating infected patients and preventing new infections. An update of the list of newly isolated specific neutralizing antibodies and suggestions for vaccine evaluation and development will be also provided.

Autoimmune disease (AID) is a condition in which the immune system breaks down and starts to attack the body. Some common AIDs include systemic lupus erythematosus, rheumatoid arthritis, type 1 diabetes mellitus and so forth. The changes in T-cell receptor (TCR) repertoire have been found in several autoimmune diseases, and may be responsible for the breakdown of peripheral immune tolerance. In this review, we discussed the processes of TCR revision in peripheral immune environment, the changes in TCR repertoire that occurred in various AIDs, and the specifically expanded T cell clones. We hope our discussion can provide insights for the future studies, helping with the discovery of disease biomarkers and expanding the strategies of immune-targeted therapy.HighlightsRestricted TCR repertoire and biased TCR-usage are found in a variety of AIDs.TCR repertoire shows tissue specificity in a variety of AID diseases.The relationship between TCR repertoire diversity and disease activity is still controversial in AIDs.Dominant TCR clonotypes may help to discover new disease biomarkers and expand the strategies of immune-targeted therapy.

More and more exosome-based therapeutics are being developed with advances in nanotechnology and precision medicine. Exosome is a kind of tiny vesicles with a bilayer of phospholipids, which can transfer biological macromolecules to recipients to influence the biological process. M2 macrophages are closely related to the occurrence and development of serious diseases such as tumor. In addition to the traditional concept of macrophage functions such as opsonization, secretion of cytokines and other soluble factors, some studies have found that the exosome derived from M2 macrophages can influence the development of disease by carrying microRNA, long noncodingRNA and functional proteins to regulate target gene expression as well as related proteins synthesis recently. Here, we outlined the biogenesis of the exosome and its biological functions in disease. Then we focused on elucidating the effects of the exosome derived from M2 macrophages on several diseases and its mechanisms. Finally, we discussed the appropriateness and inappropriateness in existing potential applications based on exosomes and macrophages.

The complement system is a multi-functional system representing the first line host defense against pathogens in innate immune response, through three different pathways. Impairment of its function, consisting in deficiency or excessive deregulated activation, may lead to severe systemic infections or autoimmune disorders. These diseases may be inherited or acquired. Despite many diagnostic tools are currently available, ranging from traditional, such as hemolytic or ELISA based assays, to innovative ones, like next generation sequencing techniques, these diseases are often not recognized. As for therapeutic aspects, strategies based on the use of targeted drugs are now widespread. The aim of this review is to present an updated overview of complement system pathophysiology, clinical implications of its dysfunction and to summarize diagnostic and therapeutic approaches.

The inflammatory immune response has evolved to protect the host from different pathogens, allergens, and endogenous death or damage-associated molecular patterns. Both innate and adaptive immune components are crucial in inducing an inflammatory immune response depending on the stimulus type and its duration of exposure or the activation of the primary innate immune response. As the source of inflammation is removed, the aggravated immune response comes to its homeostatic level. However, the failure of the inflammatory immune response to subside to its normal level generates chronic inflammatory conditions, including autoimmune diseases and cancer. Innate lymphoid cells (ILCs) are newly discovered innate immune cells, which are present in abundance at mucosal surfaces, including lungs, gastrointestinal tract, and reproductive tract. Also, they are present in peripheral blood circulation, skin, and lymph nodes. They play a crucial role in generating the pro-inflammatory immune response during diverse conditions. On the other hand, adaptive immune cells, including different types of T and B cells are major players in the pathogenesis of autoimmune diseases (type 1 diabetes mellitus, rheumatoid arthritis, psoriasis, and systemic lupus erythematosus, etc.) and cancers. Thus the article is designed to discuss the immunological role of different ILCs and their interaction with adaptive immune cells in maintaining the immune homeostasis, and during inflammatory autoimmune diseases along with other inflammatory conditions (excluding pathogen-induced inflammation), including cancer, graft-versus-host diseases, and human pregnancy.