International Reviews of Immunology最新文献

Autoimmune diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and inflammatory bowel disease (IBD) are caused by the body's immune response to autoantigens. The pathogenesis of autoimmune diseases is unclear. Numerous studies have demonstrated that RNA methylation plays a key role in disease progression, which is essential for post-transcriptional regulation and has gradually become a broad regulatory mechanism that controls gene expression in various physiological processes, including RNA nuclear output, translation, splicing, and noncoding RNA processing. Here, we outline the writers, erasers, and readers of RNA methylation, including N6-methyladenosine (m⁶A), 2'-O-methylation (Nm), 2'-O-dimethyladenosine (m⁶Am), N1-methyladenosine (m¹A), 5-methylcytidine (m⁵C) and N7-methylguanosine (m⁷G). As the role of RNA methylation modifications in the immune system and diseases is explained, the potential treatment value of these modifications has also been demonstrated. This review reports the relationship between RNA methylation and autoimmune diseases, highlighting the need for future research into the therapeutic potential of RNA modifications.

Th9 cells, a subset of T-helper cells producing interleukin-9 (IL-9), play a vital role in the adaptive immune response and have diverse effects in different diseases. Regulated by transcription factors like PU.1 and IRF4, and cytokines such as IL-4 and TGF-β, Th9 cells drive tissue inflammation. This review focuses on their emerging role in immunopathophysiology. Th9 cells exhibit immune-mediated cancer cell destruction, showing promise in glioma and cervical cancer treatment. However, their role in breast and lung cancer is intricate, requiring a deeper understanding of pro- and anti-tumor aspects. Th9 cells, along with IL-9, foster T cell and immune cell proliferation, contributing to autoimmune disorders. They are implicated in psoriasis, atopic dermatitis, and infections. In allergic reactions and asthma, Th9 cells fuel pro-inflammatory responses. Targeting Foxo1 may regulate innate and adaptive immune responses, alleviating disease symptoms. This comprehensive review outlines Th9 cells' evolving immunopathophysiological role, emphasizing the necessity for further research to grasp their effects and potential therapeutic applications across diseases.

Signal transducer and activator of transcription (STAT) 4 and STAT6 play a crucial role in immune cells by transducing signals from specific cytokine receptors, and inducing transcription of genes involved in cell-mediated and humoral immunity. These two different defense mechanisms against pathogens are regulated by two specific CD4+ T helper (Th) cells known as Th1 and Th2 cells. Many studies have shown that several diseases including cancer, inflammatory, autoimmune and allergic diseases are associated with a Th1/Th2 imbalance caused by increased or decreased expression/activity of STAT4 or STAT6 often due to genetic and epigenetic aberrances. An altered expression of STAT4 has been observed in different tumors and autoimmune diseases, while a dysregulation of STAT6 signaling pathway is frequently observed in allergic conditions, such as atopic dermatitis, allergic asthma, food allergy, and tumors such as Hodgkin and non-Hodgkin lymphomas. Recently, dysregulations of STAT4 and STAT6 expression have been observed in SARS-CoV2 and monkeypox infections, which are still public health emergencies in many countries. SARS-CoV-2 can induce an imbalance in Th1 and Th2 responses with a predominant activation of STAT6 in the cytosol and nuclei of pneumocytes that drives Th2 polarization and cytokine storm. In monkeypox infection the virus can promote an immune evasion by inducing a Th2 response that in turn inhibits the Th1 response essential for virus elimination. Furthermore, genetic variations of STAT4 that are associated with an increased risk of developing systemic lupus erythematosus seem to play a role in defense against SARS-CoV-2 infection.

Innate lymphoid cells are a mixed population of cells and critical regulators of our innate immune system. According to recent scientific literature, tissue resident innate lymphoid cell subtype 2 has been recognized as an important player of type 2 inflammatory responses, involved in different human malignancies like pancreatic, lung, acute myeloid leukemia, gastrointestinal tract cancer, etc. The current reports have revealed that, among the three main ILC sub types, subtype 2 (ILC 2), as the key regulator of initiating the type 2 inflammatory responses at the tumor microenvironment (TME). This activation of ILC-2 is a very important step for the specific downstream functioning of ILC-2. Priming of ILC-2 with different chemokines involves different cytokine secretion from the activated ILC-2 like IL-4, IL-5, IL-13, IL-9 which induce type 2 inflammatory responses involved in the complex interaction with other immune cells like NK cell, Cytotoxic T cell, MDSC and T_reg cell. At the initial stage, ILC-2 activation through IL-33 may induce the anti-tumorigenic effect mediated by ILC-2/eosinophil axis. However, it is also evident that PDG2 (Prostaglandin D2)-mediated activation of ILC-2 induces the ILC-2/MDSC immune suppressive pro-tumorigenic niche at the TME. Here, in this review, we have summarized the function of ILC-2 on cancer immunity based on recent scientific work which indicates ILC-2 plays a dual role and orchestrates the immune responses toward type 2 immunity in different cancer settings.

Cholesterol is a key life-sustaining molecule which regulates membrane fluidity and serves as a signaling mediator. Cholesterol homeostasis is closely related to various pathological conditions including tumor, obesity, atherosclerosis, Alzheimer's disease and viral infection. Viral infection disrupts host cholesterol homeostasis, facilitating their own survival. Meanwhile, the host cells strive to reduce cholesterol accessibility to limit viral infection. This review focuses on the regulation of cholesterol metabolism and the role of cholesterol in viral infection, specifically providing an overview of cholesterol as a friend to promote viral entry, replication, assembly, release and immune evasion, which might inspire valuable thinking for pathogenesis and intervention of viral infection.

Regulatory T cells (Tregs) play an important immunosuppressive role in inflammatory bowel disease (IBD). However, findings on the quantitative and functional changes of intestinal and circulating Tregs in patients with IBD are rather contradictory. We therefore conducted a meta-analysis on this issue. The pooled effect was assessed using the standardized mean difference (SMD) with a 95% confidence interval (CI), and subgroup analyses were performed to investigate heterogeneity. This analysis included 764 IBD (402 UC and 362 CD) patients and 341 healthy controls (HCs) pooled from 17 eligible studies. The percentage of circulating Tregs was significantly decreased in active IBD patients compared to HCs (SMD = -0.95, p < 0.001) and inactive IBD patients (SMD = -0.80, p < 0.001). There was no difference in the percentage of circulating Tregs between inactive IBD patients and HCs. The suppressive function of circulating Tregs was impaired in active IBD patients according to limited data (SMD = -0.75, p = 0.02). Besides, the percentage of intestinal Tregs was significantly higher in inflamed regions than in non-inflamed regions (SMD = 0.85, p < 0.001). Our study quantitatively summarized the quantitative and functional changes of Tregs and supported the therapeutic potential of Tregs in IBD. Moreover, additional research into the functions and characteristics of intestinal Tregs in IBD is needed.

Background: The gut microbiome plays a role in the development and progression of colorectal cancer (CRC).

Aim and objective: This review focuses on whether the gut microbiome is involved in the development and regulation of the host immune system.

Methods: The gut microbiome can influence the production and activity of immune cells and molecules that help to maintain the integrity of the intestinal barrier and prevent inflammation. Gut microbiota modulates the anti-cancer immune response. The gut microbiota can influence the function of immune cells, like T cells, that recognize and eliminate cancer cells. Gut microbiota can affect various aspects of cancer progression and the efficacy of various anti-cancer treatments.

Results: Gut microbiota provide promise as a potential biomarker to identify the effect of immunotherapy and as a target for modulation to improve the efficacy of immunotherapy in CRC treatment.

Conclusion: The potential synergistic effect between the gut microbiome and anti-cancer treatment modalities provides an interest in developing strategies to modulate the gut microbiome to improve the efficacy of anti-cancer treatment.

Chemokines belong to the group of small proteins within the cytokine family having strong chemo-attractant properties. In most cases, the strong immuno-modulatory role of chemokines is crucial for generating the immune response against pathogens in various protozoan diseases. In this review, we have given a brief update on the classification, characterization, homeostasis, transcellular migration, and immuno-modulatory role of chemokines. Here we will evaluate the potential role of chemokines and their regulation in various protozoan diseases. There is a significant direct relationship between parasitic infection and the recruitment of effector cells of the immune response. Chemokines play an indispensable role in mediating several defense mechanisms against infection, such as leukocyte recruitment and the generation of innate and cell-mediated immunity that aids in controlling/eliminating the pathogen. This process is controlled by the chemotactic movement of chemokines induced as a primary host immune response. We have also addressed that chemokine expressions during infection are time-dependent and orchestrated in a systematic pattern that ultimately assists in generating a protective immune response. Taken together, this review provides a systematic understanding of the complexity of chemokines profiles during protozoan disease conditions and the rationale of targeting chemokines for the development of therapeutic strategies.

Autoimmune diseases are characterized by a breakdown of immune tolerance, leading to inflammation and irreversible end-organ tissue damage. Platelet extracellular vesicles are cellular elements that are important in blood circulation and actively participate in inflammatory and immune responses through intercellular communication and interactions between inflammatory cells, immune cells, and their secreted factors. Therefore, platelet extracellular vesicles are the "accelerator" in the pathological process of autoimmune diseases; however, this robust set of functions of platelet extracellular vesicles has also prompted new advances in therapeutic strategies for autoimmune diseases. In this review, we update fundamental mechanisms based on platelet extracellular vesicles communication function in autoimmune diseases. We also focus on the potential role of platelet extracellular vesicles for the treatment of autoimmune diseases. Some recent studies have found that antiplatelet aggregation drugs, specific biological agents can reduce the release of platelet extracellular vesicles. Platelet extracellular vesicles can also serve as vehicles to deliver drugs to targeted cells. It seems that we can try to silence or inhibit microRNA carried by platelet extracellular vesicles transcription and regulate the target cells to treat autoimmune diseases as platelet extracellular vesicles can transfer microRNA to other cells to regulate immune-inflammatory responses. Hopefully, the information presented here will provide hope for patients with autoimmune diseases.