International Reviews of Immunology最新文献

Several risk factors are known to be involved in the initiation and development of gastric cancer. Among them, H. pylori is one of the most prominent with multiple virulence factors contributing to its pathogenicity. In this study, we have discussed an interesting immunological cycle exploring the interplay between H. pylori, aryl hydrocarbon receptor (AHR), tryptophan, arginine, and the metabolites of these two amino acids in the development of gastric cancer. AHR is a ligand-activated transcription factor which acts as a regulator for a diverse set of genes and has various types of exogenous and endogenous ligands. The tryptophan metabolite, kynurenine, is one of these ligands that can interact with AHR, leading to immune suppression and subsequently, susceptibility to gastric cancer. On the other hand, H. pylori downregulates the expression of AHR and AHR repressor (AHRR), leading to increased inflammatory cytokine production. A metabolite of the kynurenine pathway, xanthurenic acid, is a potent inhibitor of a terminal enzyme in the synthetic pathway of tetrahydrobiopterin (BH4). BH4, itself, is a cofactor in the process of nitric oxide (NO) production from arginine that has been shown to have immune-enhancing properties. Arginine has also been evidenced to have anti-tumoral function through inducing apoptosis in gastric cell lines; however, controversy exists regarding the anti-tumor role of arginine and BH4, since they are also associated with increased NO production, subsequently promoting tumor angiogenesis. Hence, although several synergistic connections result in immunity improvement, these correlations can also act as a double-edged sword, promoting tumor development. This emphasizes on the need for further investigations to better understand this complex interplay.

Indoleamine 2, 3-dioxygenase (IDO) as an intracellular cytosolic enzyme converts tryptophan (Trp) to N-formyl kynurenine which leads to proinflammatory T-cell apoptosis and prevention of immune cells maturation via decreasing the level of cellular energy. Trp catabolism products such as kynurenine increase the recruitment of regulatory T cells and induce immune tolerance in dendritic cells. IDO expression can locally suppress immunity in the tumor microenvironment and tumor progression actively recruits IDO expressing cells in tumor-draining lymph nodes. Also, tumor infiltrating Tregs' activity leads to IDO expression in the tumor microenvironment. In this review, we described the immunomodulatory function of IDO and IDO-based therapeutic strategies for immune related diseases. According to positive-feedback loop between Tregs and IDO in the tumor microenvironment, IDO can be targeted as a promising immunostimulatory approach for immunotherapy of cancer. However, several studies revealed controversial consequences for influences of IDO in immunity. Considering the common concept, IDO1 and also IDO2 repress the function of T lymphocytes, while inactivation of IDO results in aggravation of some autoimmune diseases. Eventually, the extensive evaluation of IDO function in immunomodulatory procedure can help achieve IDO inhibitors as optimal drugs to inhibit tumor growth without motivating autoimmunity.

The immune system response of transplant recipients is the main cause of allograft rejection; therefore, its suppression seems crucial. Nevertheless, immunosuppressive agents are largely ineffective against innate immune response. Innate immunity is immediately activated after transplantation and contribute to allograft inflammation and rejection. In this regard, understanding the mechanism of activation and targeting the components of innate immunity could improve allograft survival time. In this review, we discuss two scenarios in the innate immunity, i.e., danger and allogeneic signals in the context of both allogeneic and syngeneic graft. Moreover, the mechanisms of innate allorecognition (i.e., signal regulatory protein α-CD47 and paired immunoglobulin-like receptors-MHC I axis) are described, which can improve our clinical decisions to use a better therapeutic strategy.

Immunological memory is critical for host immunity and decisive for individual to respond exponentially to previously encountered infection. Both T and B cell memory are known to orchestrate immunological memory with their central and effector memory arms contributing in prolonged immunity/defence mechanisms of host. While central memory helps in maintaining prolonged immunity for a particular infection, effector memory helps in keeping local/seasonal infection in control. In addition to this, generation of long-lived plasma cells is pivotal for generating neutralizing antibodies which can enhance recall and B cell memory to control re-infection. In view of this, scaling up memory response is one of the major objectives for the expected outcome of vaccination. In this line, this review deals with the significance of memory cells, molecular pathways of their development, maintenance, epigenetic regulation and negative regulation in various infections. We have also highlighted the significance of both T and B cell memory responses in the vaccination approaches against range of infections which is not fully explored so far.[Box: see text].

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.

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.

Objective: Human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule involved in inducing tolerance at the feto-maternal interface and in escape of immune response by tumor cells. The aim of the study is to review the published literature on the expression of HLA-G in malignant melanomas and its clinicopathological and prognostic correlates.

Methods: A systematic search was carried out in electronic databases. Studies dealing with HLA-G expression in surgically-removed human samples were retrieved and analyzed.

Results: Of 1737 retrieved articles, 16 were included. The main themes regarded HLA-G expression in malignant melanocytic lesions, assessed by immunohistochemistry (IHC), soluble or molecular techniques, and its relationship with clinicopathological features, such as tumor thickness and malignant behavior. Overall significant HLA-G expression was found in 460/843 tumors (55%), and specifically in 251/556 melanomas (45%) evaluated with IHC, in 208/250 cases (83%) examined with soluble methods and in 13/23 melanoma lesions (57%) tested with polymerase chain reaction. Despite the correlation with parameters indicating an aggressive behavior, no studies demonstrated any prognostic value of HLA-G expression. Furthermore, uveal melanomas were constantly negative for this biomarker.

Conclusion: Overall, published data indicate that while HLA-G is involved in the interactions between melanomas and the immune system, it is unlikely to be the only factor to play such a role, therefore making it difficult to designate it as a prognostically relevant molecule. Evidence further suggests that HLA-G is not implicated in the immunobiology of uveal melanomas.