International Reviews of Immunology最新文献

Human cytomegalovirus (HCMV) is a representative β-herpesvirus that establishes persistent infections in humans, and exhibits high seropositivity rates in adults. It has co-evolved with its human host and employs various strategies to evade antiviral mechanisms by utilizing a significant portion of its genome. HCMV-encoded proteins and miRNAs have been implicated in regulating these mechanisms, enabling viral survival within the human body. During viral infections, autophagy, a conserved catabolic process essential for cellular homeostasis, acts as an antiviral defense mechanism. Multiple studies have reported that HCMV can modulate autophagy through its proteins and miRNAs, thereby influencing its survival within the host. In this study, we showed the potential involvement of HCMV miRNAs in cellular autophagy. We employed various bioinformatic tools to predict putative HCMV miRNAs that target autophagy-related genes and their corresponding cellular autophagy genes. Our results show that the 3'UTR of autophagy-related genes, including ATG9A, ATG9B, ATG16L2, SQSTM1, and EIF2AK2, harbors potential binding sites for hcmv-miR-UL70-3p. Experimental manipulation involving ectopic expression of hcmv-miR-UL70-3p demonstrated a significant reduction in rapamycin-induced autophagy, with ATG9A as its functional target. These findings establish that hcmv-miR-UL70-3p acts as an autophagy inhibitor by suppressing the expression of ATG9A.

The immune system has a substantial impact on the growth and expansion of lung malignancies. Immune cells are encompassed by a stroma comprising an extracellular matrix (ECM) and different cells like stromal cells, which are known as the tumor immune microenvironment (TIME). TME is marked by the presence of immunosuppressive factors, which inhibit the function of immune cells and expand tumor growth. In recent years, numerous strategies and adjuvants have been developed to extend immune responses in the TIME, to improve the efficacy of immunotherapy. In this comprehensive review, we outline the present knowledge of immune evasion mechanisms in lung TIME, explain the biology of immune cells and diverse effectors on these components, and discuss various approaches for overcoming suppressive barriers. We highlight the potential of novel adjuvants, including toll-like receptor (TLR) agonists, cytokines, phytochemicals, nanocarriers, and oncolytic viruses, for enhancing immune responses in the TME. Ultimately, we provide a summary of ongoing clinical trials investigating these strategies and adjuvants in lung cancer patients. This review also provides a broad overview of the current state-of-the-art in boosting immune responses in the TIME and highlights the potential of these approaches for improving outcomes in lung cancer patients.

Type 17 T helper (Th17) cells, which are a subtype of CD4⁺ T helper cells, secrete pro-inflammatory cytokines such as IL-17A, IL-17F, IL-21, IL-22, and GM-CSF, which play crucial roles in immune defence and protection against fungal and extracellular pathogen invasion. However, dysfunction of Th17 cell immunity mediates inflammatory responses and exacerbates tissue damage. This pathological process initiated by Th17 cells is common in kidney diseases associated with renal injury, such as glomerulonephritis, lupus nephritis, IgA nephropathy, hypertensive nephropathy, diabetic kidney disease and acute kidney injury. Therefore, targeting Th17 cells to treat kidney diseases has been a hot topic in recent years. This article reviews the mechanisms of Th17 cell-mediated inflammation and autoimmune responses in kidney diseases and discusses the related clinical drugs that modulate Th17 cell fate in kidney disease treatment.

Systemic lupus erythematosus (SLE), an autoimmune condition, presents pregnancy-related risks, impacting maternal and fetal health. The immune cell composition and gene expression profiles in pregnant SLE patients, as well as the molecular mechanisms of active SLE patients during pregnancy, remain unclear. In our study, we enrolled 12 patients: three active SLE individuals (SLE-AT group, SLEDAI > 12, non-pregnant women), three inactive SLE individuals (SLE-NP group, SLEDAI ranging 0 to 6, non-pregnant women), three pregnant women with active SLE (SLE-C group, SLEDAI > 12), and three pregnant women with inactive SLE (SLE-NC group, SLEDAI range 0 to 6 score). Transcriptome analysis of peripheral blood mononuclear cells (PBMCs) was conducted using the 10x Genomics technique. We observed upregulation of genes like CCDC15 and TRBV4-2 in T cells and CMPK2, IFIT1, and OAS2 in monocytes in the SLE-C group. Notably, gene sets related to Cell Cycle and IFN Response showed significant differences between the SLE-C and SLE-NC groups in naïve CD8 T cells. Our comparison of immune cell type ratios and transcriptional patterns between active and inactive SLE during pregnancy sheds light on the single-cell level changes in SLE status during pregnancy, offering insights for future SLE prediction and treatment strategies.

Computational biology involves applying computer science and informatics techniques in biology to understand complex biological data. It allows us to collect, connect, and analyze biological data at a large scale and build predictive models. In the twenty first century, computational resources along with Artificial Intelligence (AI) have been widely used in various fields of biological sciences such as biochemistry, structural biology, immunology, microbiology, and genomics to handle massive data for decision-making, including in applications such as drug design and vaccine development, one of the major areas of focus for human and animal welfare. The knowledge of available computational resources and AI-enabled tools in vaccine design and development can improve our ability to conduct cutting-edge research. Therefore, this review article aims to summarize important computational resources and AI-based tools. Further, the article discusses the various applications and limitations of AI tools in vaccine development.

Mesenchymal Stromal/Stem Cells (MSCs) are multipotent, non-hematopoietic progenitor cells with a wide range of immune modulation and regenerative potential which qualify them as a potential component of cell-based therapy for various autoimmune/chronic inflammatory ailments. Their immunomodulatory properties include the secretion of immunosuppressive cytokines, the ability to suppress T-cell activation and differentiation, and the induction of regulatory T-cells. Considering this and our interest, we here discuss the significance of MSC for the management of Graft-versus-Host-Disease (GvHD), one of the autoimmune manifestations in human. In pre-clinical models, MSCs have been shown to reduce the severity of GvHD symptoms, including skin and gut damage, which are the most common and debilitating manifestations of this disease. While initial clinical studies of MSCs in GvHD cases were promising, the results were variable in randomized studies. So, further studies are warranted to fully understand their potential benefits, safety profile, and optimal dosing regimens. Owing to these inevitable issues, here we discuss various mechanisms, and how MSCs can be employed in managing GvHD, as a cellular therapeutic approach for this disease.

With the change in global environment, respiratory disorders are becoming more threatening to the health of people all over the world. These diseases are closely linked to performance of immune system. Within the innate arm of immune system, Neutrophils are an important moiety to serve as an immune defense barrier. They are one of the first cells recruited to the site of infection and plays a critical role in pathogenesis of various pulmonary diseases. It is established that the migration and activation of neutrophils can lead to inflammation either directly or indirectly and this inflammation caused is very crucial for the clearance of pathogens and resolution of infection. However, the immunopathological mechanisms involved to carry out the same is very complex and not well understood. Despite there being studies concentrating on the role of neutrophils in multiple respiratory diseases, there is still a long way to go in order to completely understand the complexity of the participation of neutrophils and mechanisms involved in the development of these respiratory diseases. In the present article, we have reviewed the literature to comprehensively provide an insight in the current development and advancements about the role of neutrophils in infectious respiratory disorders including viral respiratory disorders such as Coronavirus disease (COVID-19) and bacterial pulmonary disorders with a focused review on pulmonary tuberculosis as well as in noninfectious disorders like Chronic obstructive pulmonary disease (COPD) and asthma. Also, future directions into research and therapeutic targets have been discussed for further exploration.

Salivary glands naturally play central roles in oral immunity. The salivary glands microenvironment inevitable may be exposed to exogenous factors consequently triggering the initiation and formation of various malignant and benign tumors. Mesenchymal stem cells are recruited into salivary gland microenvironment, interact with tumor cells, and induce inhibitory cytokines as well as cells with immunosuppressive phenotypes such as myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs). The immune components and tumor immune responses in malignant and benign SGTs are still under investigation. Immune responses may directly play a limiting role in tumor growth and expansion, or may participate in formation of a rich milieu for tumor growth in cooperation with other cellular and regulatory molecules. Immune checkpoint molecules (e.g. PDLs, HLA-G and LAG3) are frequently expressed on tumor cells and/or tumor-infiltrating lymphocytes (TILs) in salivary gland microenvironment, and an increase in their expression is associated with T cell exhaustion, immune tolerance and tumor immune escape. Chemokines and chemokine receptors have influential roles on aggressive behaviors of SGTs, and thereby they could be candidate targets for cancer immunotherapy. To present a broad knowledge on salivary glands, this review first provides a brief description on immunological functions of normal salivary glands, and then describe the SGT's tumor microenvironment, by focusing on mesenchymal stem cells, immune cell subsets, immune checkpoint molecules, chemokines and chemokine receptors, and finally introduces immune checkpoint inhibitors as well as potential targets for cancer therapy.

The intestinal mucosa is an important structure involved in resistance to pathogen infection. It is mainly composed of four barriers, which have different but interrelated functions. Pathogenic bacteria can damage these intestinal mucosal barriers. Here, we mainly review the mechanisms of pathogen damage to biological barriers. Most γδ T cells are located on the surface of the intestinal mucosa, with the ability to migrate and engage in crosstalk with microorganisms. Commensal bacteria are involved in the activation and migration of γδ T cells to monitor the invasion of pathogens. Pathogen invasion alters the migration pattern of γδ T cells. γδ T cells accelerate pathogen clearance and limit opportunistic invasion of commensal bacteria. By discussing these interactions among γδ T cells, commensal bacteria and pathogenic bacteria, we suggest that γδ T cells may link the interactions between commensal bacteria and pathogenic bacteria.

The thymus is a primary lymphoid organ, essential for the development of T-cells that will protect from invading pathogens, immune disorders, and cancer. The thymus decreases in size and cellularity with age referred to as thymus involution or atrophy. This involution causes decreased T-cell development and decreased naive T-cell emigration to the periphery, increased proportion of memory T cells, and a restricted, altered T-cell receptor (TCR) repertoire. The changes in composition and function of the circulating T cell pool as a result of thymic involution led to increased susceptibility to infectious diseases including the recent COVID and a higher risk for autoimmune disorders and cancers. Thymic involution consisting of both structural and functional loss of the thymus has a deleterious effect on T cell development, T cell selection, and tolerance. The mechanisms which act on the structural (cortex and medulla) matrix of the thymus, the gradual accumulation of genetic mutations, and altered gene expressions may lead to immunosenescence as a result of thymus involution. Understanding the molecular mechanisms behind thymic involution is critical for identifying diagnostic biomarkers and targets for treatment help to develop strategies to mitigate thymic involution-associated complications. This review is focused on the consequences of thymic involution in infections, immune disorders, and diseases, identifying potential checkpoints and potential approaches to sustain or restore the function of the thymus particularly in elderly and immune-compromised individuals.