Acta biochimica et biophysica Sinica最新文献

Intestinal immunosenescence, a hallmark of organismal aging, has emerged as a critical biological process impacting the health of elderly individuals. This review systematically examines the core mechanisms underlying intestinal immunosenescence, including immune cell dysfunction, imbalances in immune-microbiota interactions, and impaired barrier function. We analyze its associations with infectious diseases, chronic inflammation, and neurodegenerative disorders, summarizing recent advances in dietary interventions, microecological therapy, and other emerging strategies. By integrating cutting-edge technologies, we prospect the development of precision interventions aimed at delaying intestinal immunosenescence, thereby providing a theoretical basis for improving the healthspan of the aging population.

Over the past decade, immunotherapy has emerged as a pivotal therapeutic strategy in cancer treatment. Immune checkpoint inhibitors (ICIs), such as CTLA-4 and PD-1 monoclonal antibodies, have demonstrated remarkable clinical efficacy in different types of cancer. However, the overall success rate of immune checkpoint therapies remains low. Investigating alternative immune checkpoint molecules is imperative. T-cell immunoglobulin and mucin-containing molecule-3 (TIM-3), which is expressed in T cells, natural killer (NK) cells, macrophages, and dendritic cells, has gained recognition as a promising candidate for tumor immunotherapy. Targeting TIM-3 represents a promising approach for cancer immunotherapy, particularly through the rational design of novel combination therapies with other ICIs. In this review, we present a comprehensive summary of the research advancements concerning the role of TIM-3 in regulating immune responses in different cell types and explore theoretical frameworks for targeting TIM-3 to achieve more effective immunotherapeutic breakthroughs.

Group 2 innate lymphoid cells (ILC2s), a subset of innate lymphoid cells (ILCs) lacking antigen-specific receptors and functionally mirroring T helper 2 (Th2) cells, are indispensable components of the innate immune system that lack antigen-specific receptors but phenotypically and functionally mirror T helper 2 (Th2) cells, particularly in their expression of the transcription factor GATA3 and the secretion of type 2 cytokines for mediating type 2 immune responses. ILC2s are tissue-resident cells in mucosal tissues, including the lung, where they play crucial roles in maintaining tissue homeostasis and regulating immune responses. ILC2s are poised to respond to environmental signals such as IL-25, IL-33, and TSLP, which activate and expand ILC2s. Their functions are highly context-dependent and influenced by interactions with other immune cells. In this review, we summarize recent findings on the roles of ILC2s in lung diseases, highlighting their typical characteristics and their responsiveness to environmental signals in the context of pulmonary pathology. We also discuss potential therapeutic strategies targeting ILC2s, which may offer new avenues for the treatment of inflammatory lung diseases. Understanding the mechanisms by which ILC2s contribute to lung disease progression will provide valuable insights for the development of novel diagnostic ( e. g., ILC2 phenotypic markers) and therapeutic approaches ( e. g., targeting ILC2 plasticity or alarmin-ILC2 signaling axes).

This review synthesizes how neurotransmitters-including glutamate, acetylcholine (ACh), γ-aminobutyric acid (GABA), serotonin (5-HT), and catecholamines-modulate T-cell immunity in the tumor microenvironment through activation, differentiation, trafficking, and checkpoint dependence. Glutamate amplifies T-cell receptor signaling but is counterbalanced by tumor-derived glutamate export. Cholinergic pathways exert dual effects through nicotinic and muscarinic receptors, whereas GABA generally imposes metabolic and signaling brakes that favor regulatory programs. Serotonin shows spatial divergence-suppressing peripheral responses but enhancing intratumoral cytotoxicity-and chronic β-adrenergic stress dampens effector function and limits immunotherapy efficacy. Advances in spatial multi-omics, single-cell profiling, and neuromodulation will help discover new targets across these axes. This review provides mechanistic insights and translational implications, highlighting emerging strategies such as glutamate receptor, metabotropic glutamate receptor 4 (mGluR4) or xCT (SLC7A11) inhibition, receptor subtype modulation, and β-blockade. Integrating neurotransmitter-receptor targeting with checkpoint inhibitors or cell therapies may improve the depth and durability of cancer immunotherapy.

Reductive stress is characterized by the excessive accumulation of cellular reducing equivalents, leading to the disruption of cellular redox homeostasis and a shift toward a reductive intracellular environment. Immune cells exhibit particularly dynamic redox modulation to adapt to activation and differentiation processes during immune responses, such as tumor recognition and destruction. Unlike their immune counterparts, tumor cells employ a specific metabolic mode for uncontrolled proliferation and survival, which may also lead to a shift in the intracellular redox balance. While extensive research has focused on oxidative stress during the immune response and cancer treatment, studies on reductive stress are still in their infancy. This review summarizes the generation process of reductive stress and its impact on cellular function, detailing its mechanisms in immune cells and various cancers, as well as its relevance to cancer treatment. The aim of this study is to explore new avenues for cancer immunotherapy from the perspective of reductive stress.

Macrophages are well known for their widespread distribution, diverse roles, and involvement in multiple pathophysiological contexts, thereby constructing an immunological front line. Meanwhile, constant efforts over the past few decades have unveiled diverse reprogramming patterns of lipid metabolism as crucial, response- and context-specific drivers of macrophage functions and fate. Here, we take a bird's-eye view of major fields across the research landscape of lipid-regulated macrophages; review the latest advances in understanding how alterations in several lipid subclasses, especially their fatty acyl composition and oxidative status, direct macrophage-mediated responses and pathology outcomes; and summarize representative insights that have deciphered the lipidome composition of macrophages or profiled specific lipid species under different scenarios. We hope that this review provides readers with a handy grip to learn and explore the field of lipid-regulated immunobiology, exemplified by but not limited to macrophages.

Emerging studies have revealed that disruptions in circadian crosstalk between the gut microbiota and the host play an essential role in the pathogenesis of metabolic disorders. Under physiological conditions, host circadian clocks regulate microbial diurnal oscillations through rhythmic behaviors, including feeding patterns and sleep-wake cycles. This temporal regulation manifests as robust 24-hour oscillations in microbial community composition, spatial organization, and metabolic activity. These rhythmic microbial signals and their metabolic outputs are subsequently translated into host immune modulation, establishing a bidirectional temporal dialogue between the host and microbiota. Modern lifestyle disruptions, including erratic eating patterns and shift work, desynchronize this temporal dialogue, leading to the loss of microbial rhythms, impaired intestinal barrier function, maladaptive immune responses, chronic inflammation, and systemic metabolic dysregulation. This review delineates the mechanisms through which host-microbiota circadian crosstalk governs immunometabolic homeostasis, provides a mechanistic framework for understanding immunometabolic diseases, and highlights therapeutic strategies that target microbial rhythms to reset host immunity and metabolism.

Gut inflammatory diseases, including inflammatory bowel disease (IBD), infectious enteritis, and other inflammatory conditions, are among the most common non-neoplastic intestinal disorders. Their pathogenesis is often driven by an imbalance between pro-inflammatory and anti-inflammatory signals, with immune cells playing pivotal roles in maintaining this equilibrium. Immune cells in the gut exhibit complex, multifaceted functions: they eliminate pathogens, promote tissue repair, and counteract tumors, but excessive immune activation can exacerbate tissue damage and disease progression. Notably, metabolic reprogramming in inflammatory contexts serves as a key regulator of immune cell function and phenotypic switching. This includes alterations in cellular energy metabolism ( e. g., macrophage polarization via disrupted glycolysis or fatty acid oxidation) and the modulation of immune responses by microenvironmental metabolites ( e. g., bile acid-mediated Th17/Treg balance). While alterations in immune cell function and composition within the inflammatory milieu are well-established, the significance of disease-associated metabolic reprogramming-specifically how metabolism regulates immune cell function-has garnered increasing attention. This review explores how cellular metabolic reprogramming, changes in the metabolic microenvironment, and gut dysbiosis collectively influence the differentiation, proliferation, and function of immune cells in various intestinal inflammatory diseases, as well as their impact on disease progression.

Immunotherapy, including cellular therapy, has emerged as a crucial pillar in cancer treatment, complementing established modalities such as surgery, chemotherapy and radiotherapy. The clinical observation that immunotherapy is effective in only a limited proportion of patients inspires mechanistic research on the complicated regulatory network within the tumor microenvironment (TME). Circadian regulation significantly affects immune cell behavior, including the activity of immune cells and cytokine production, and emerging evidence suggests the key role of circadian regulation in the TME, which subsequently affects the effectiveness of immunotherapy. Results from preclinical and clinical studies indicate that appropriate timing of adoptive cellular therapy and immune checkpoint blockade therapy improves their efficacy. Therefore, understanding the molecular mechanism of the circadian rhythm together with its role in immunotherapy is essential for optimizing cellular function, proliferation and persistence in the TME. Here, we review how circadian rhythms influence immunotherapy and the TME across different stages of tumor progression. Future clinical protocols may integrate concepts of circadian rhythm and immunotherapy to enhance treatment response.