International Reviews of Immunology最新文献

Since its first clinical application, 120 years ago, radiotherapy evolved into a major anti-cancer treatment modality, offering high cure rates in many human malignancies. During the past ten years, the establishment of immune checkpoint inhibitors (ICIs) in cancer therapeutics has vigorously reintroduced the immune system's role in the outcome of radiotherapy and, conversely, the role of radio-vaccination in the efficacy of immunotherapy. The knowledge and clinical experience that founded the current era of immuno-radiotherapy started alongside with the birth of radiotherapy, and evolved through exhaustive experimental work, clinical trials on active specific immunotherapy, frustrating attempts to validate the importance of cytokine administration with radiotherapy, and, finally, the encouraging ICI-based clinical trials that opened the door to a far more encouraging perspective; radio-vaccination, through its old and new methods, is rising as a research field that promises to cure, previously incurable, disease. In this critical review, we focus on the scientific knowledge gathered through more than a century of research on radiotherapy interactions with the immune system. Understanding the origins of this promising therapeutic approach will substantially contribute to developing new immuno-radiotherapy policies in the fight against cancer.

Accumulating data emphasize a strong link between obesity and the severity of coronavirus disease-2019 (COVID-19), including mortality. Obesity interferes with several components of the immune system including lymphoid tissue's integrity, leukocytes' development and function, complement system's activation, and the coordination of innate and adaptive immune responses. Overall, obesity results in a less efficient immune response to infectious agents. Severe acute respiratory syndrome coronavirus 2 exploits this weakened immune system in people with obesity to precipitate COVID-19, and in some cases death. It is therefore the author's recommendation that obesity should be viewed as another form of acquired immunodeficiency syndrome and be treated with the appropriate seriousness. Unlike the previously described acquired immunodeficiency syndrome (AIDS) that is caused by the Human Immunodeficiency Virus (HIV), obesity is a comorbidity-acquired immunodeficiency syndrome. People with AIDS do not die from HIV, but may die from opportunistic pathogens such as Mycobacterium tuberculosis. However, AIDS is ascribed its due importance in the course of deterioration of the patient. Similarly, obesity should be acknowledged further as a risk factor for mortality from COVID-19. Obesity is a modifiable condition and even in people with a strong genetic predisposition, lifestyle modifications can reverse obesity, and even moderate weight loss can improve the inflammatory milieu. Strong public health actions are warranted to promote lifestyle measures to reduce the burden from overweight and obesity that currently affect more than one-third of the global population, with projections alarming this may reach 55-80% within the next thirty years.

Metabolism could be served as a guiding force for immunity, and macrophages undergo drastic metabolic reprogramming during inflammatory processes, including enhancing glycolysis and reshaping the tricarboxylic acid cycle (TCA) cycle. The disrupted TCA cycle facilitates itaconate accumulation, consistent with the significant up-regulation of immune response gene 1 (IRG1) in activated macrophages. IRG1 catalyzes the decarboxylation of cis-aconitate to synthesize itaconate, and notably, the IRG1-Itaconate axis has excellent potential to link macrophages' immunity and metabolism. Here, we review vital molecules that affect the activation of the IRG1-Itaconate axis, including interferon regulatory factor 1/9 (IRF1/9), transcription 1 and 3 (STAT1/3), CCAAT enhancer-binding protein β (C/EBPβ), and the protein kinase C (PKC). We then focus on how the IRG1-Itaconate axis regulates the inflammatory pathway in macrophages, proposed to involve kelch-like ECH-associated protein 1 (Keap1), NOD-, LRR- and pyrin domain-containing 3 (NLRP3), gasdermin D (GSDMD), activating transcription factor 3 (ATF3), receptor-interacting protein kinase-3 (RIPK3), et al. In addition, we provide an overview of the way the axis participates in the metabolism of macrophages. Eventually, we summarize current connections between the IRG1-Itaconate axis and inflammatory diseases, bringing light to new therapeutic opportunities in inflammatory diseases.

Exosomes are widely distributed extracellular vesicles (EVs), which are currently a major research hotspot for researchers based on their wide range of sources, stable membrane structure, low immunogenicity, and containing a variety of biomolecules. A large number of literatures have shown that exosomes and exosome cargoes (especially microRNAs) play an important role in the activation of inflammation, development of tumor, differentiation of cells, regulation of immunity and so on. Studies have found that exosomes can stimulate the immune response of the body and participate in the occurrence and development of various diseases, including autoimmune diseases. Furthermore, the potential of exosomes as therapeutic tools in various diseases has also attracted much attention. Autoimmune thyroid disease (AITD) is one of the most common autoimmune diseases, mainly composed of Graves' disease (GD) and Hashimoto's thyroiditis (HT), which affects the health of many people and has a genetic predisposition, but its pathogenesis is still being explored. Starting from the relevant biological characteristics of exosomes, this review summarizes the current research status of exosomes and the association between exosomes and some diseases, with a focus on the situation of AITD and the potential role of exosomes (including substances in their vesicles) in AITD in combination with the current published literature, aiming to provide new directions for the pathogenesis, diagnosis or therapy of AITD.Supplemental data for this article is available online at.

Epigenetic regulators are pivotal factors that influence and control T cell development. Recent findings continue to reveal additional elements of epigenetic modifications that play significant and crucial roles at different stages of T cell development. Through gaining a better understanding of the various epigenetic factors that influence the formation and survival of maturing T cells, new therapies can potentially be developed to combat diseases caused by dysregulated epigenetic chromatin modifications. In this review, we summarize the recent studies which shed light on the epigenetic regulation of T cell development especially at the critical stage of β-selection.

Celiac disease (CD) is an autoimmune disease that occurs in genetically predisposed individuals following the ingestion of gluten. Its prevalence is rising worldwide. A gluten-free (GF) diet is mandatory for the management of CD. However, several issues persist regarding the nutritional quality of GF products. Importantly, deep knowledge about the pathogenic mechanisms in CD highlights the central role of CD4⁺ T cell-mediated immunity in CD. Furthermore, intestinal T regulatory cells are functional in CD, but cytokines such as IL-15, produced under inflammatory conditions, hamper their activity. This paves the way for the development of immunomodulatory strategies to the GF diet. From this perspective, microbiological approaches were considered able to modulate the gluten-specific immune response. Interestingly, gliadin peptide-based immunotherapy to abolish the inflammatory CD4⁺T cell-mediated response has been explored in CD patients. Furthermore, different biotechnological approaches based on the use of chemically/enzymatically modified gluten molecules have been proved effective in different models of CD. However, the choice of the right age in infants to introduce the antigen and thus induce tolerance still remains an important issue to solve. Addressing all these points should help to design an effective intervention strategy for preventing CD.

Rising obesity levels, worldwide, are resulting in substantial increases in cardiovascular disease, diabetes, kidney disease, musculoskeletal disorders, and certain cancers, and obesity-associated illnesses are estimated to cause ∼4 million deaths worldwide per year. A common theme in this disease epidemic is the chronic systemic inflammation that accompanies obesity. CD4⁺ Foxp3⁺ regulatory T cells residing in visceral adipose tissues (VAT Tregs) are a unique immune cell population that play essential functions in restricting obesity-associated systemic inflammation through regulation of adipose tissue homeostasis. The distinct transcriptional program that defines VAT Tregs has been described, but directly linking VAT Treg differentiation and function to improving insulin sensitivity has proven more complex. Here we review new findings which have clarified how VAT Tregs differentiate, and how distinct VAT Treg subsets regulate VAT homeostasis, energy expenditure, and insulin sensitivity.

Primary immunodeficiency (PID) or Inborn errors of immunity (IEI) refers to a heterogeneous group of disorders characterized by immune system impairment. Although patients with IEI manifest highly variable symptoms, the most common clinical manifestations are recurrent infections, autoimmunity and malignancies. Some patients present hematological abnormality including thrombocytopenia due to different pathogenic mechanisms. This review focuses on primary and secondary thrombocytopenia as a complication, which can occur in IEI. Based on the International Union of Immunological Societies phenotypic classification for IEI, the several innate and adaptive immunodeficiency disorders can lead to thrombocytopenia. This review, for the first time, describes manifestation, mechanism and therapeutic modalities for thrombocytopenia in different classes of IEI.