Trends in Immunology最新文献

Early antibiotic exposure disrupts the gut microbiota, impairing newborn antiviral immunity. Stevens et al. uncover that inosine, a metabolite produced by gut bacteria, restores the function of antiviral T cells by modulating gene regulation, boosting lung immune defenses against respiratory viruses.

Metabolic reprogramming and signaling are key orchestrators of T cell immunity. Recent studies have illustrated important roles for intracellular organelles, especially mitochondria and lysosomes, in enforcing T cell metabolism and signaling in response to various extracellular cues. As such, mitochondrial and lysosomal function contributes to adaptive immunity by regulating T cell activation, differentiation, and functional adaptation. In this Review, we discuss how the interplay between organelle biology and metabolism instructs T cell-mediated immunity, with a particular focus on mitochondria and lysosomes. We also summarize how mitochondria and lysosomes, or their crosstalk with other organelles, orchestrate downstream signaling processes and functional reprogramming of T cells. We conclude with a discussion of the pathophysiological outcomes associated with dysregulation of these organelles.

Neuro-immune crosstalk regulates inflammation and host metabolism via neural modulation of innate lymphoid cells (ILCs). Significant knowledge gaps remain regarding the signaling pathways, regulators, and physiological relevance of these interactions in human health and disease. Future studies leveraging innovative tools promise new insights and therapies for inflammatory and metabolic diseases.

Pharmacological activation of the stimulator of interferon genes (STING) pathway triggers inflammatory innate immune responses to potentially reinvigorate tumor immunogenicity. Recent work by Dang et al. revealed an alternative paradigm: a clinically approved old drug was repurposed to boost STING signaling and immune activation via a mode of action distinct from that of conventional STING agonists.

CD8⁺ T cells, traditionally recognized for their cytotoxic role in eliminating infections and malignancies, are now known to exhibit significant functional heterogeneity, as revealed by single-cell genomics. Among these, granzyme-K-expressing (GZMK⁺) CD8⁺ T cells represent a distinct subset characterized by low cytotoxicity but heightened proinflammatory activity, by contrast with their granzyme-B-expressing (GZMB⁺) counterparts with high cytotoxicity. GZMK⁺CD8⁺ T cells are often more abundant in inflammatory diseases, cancer, and age-related inflammation (inflammaging). These cells interact with stromal cells, activate the complement cascade, and perpetuate inflammation, highlighting their emerging therapeutic significance. We review the latest advances in the biology and pathological roles of GZMK⁺CD8⁺ T cells, and discuss the potential of targeting their dysregulated activities to treat chronic inflammation and malignancies.

Communication between the gut microbiota and host post-translational modifications (PTMs) has been extensively characterized, and recent evidence delineates a functionally integrated gut microbiota-host PTM axis. This axis is not only essential for maintaining metabolism homeostasis but also plays diverse roles in regulating disease pathogenesis. In this review we discuss the emerging effects of microbial modulation of host PTMs by regulating substrate provisioning and enzyme activity. We also highlight the latest understanding of diverse microbiota-regulated PTMs in immune cell fate decision. Finally, we summarize the current understanding of how dysbiosis-induced PTM dysregulation drives pathologies in inflammatory bowel disease (IBD), obesity-related diseases, rheumatoid arthritis (RA), chronic kidney disease (CKD), and colorectal cancer (CRC). We also propose targeted strategies to restore homeostasis through the microbiota-PTM axis.

Macrophages are sentinels and first responders of the innate immune system. By sensing danger signals, they initiate and amplify inflammatory and regenerative cascades to control appropriate responses to pathogens and tissue damage. Transcriptional activation of macrophage gene expression has been studied extensively, but macrophage responses also rely on regulation of mRNAs following transcription. In this review we discuss mechanisms of post-transcriptional regulation that alter macrophage gene expression programs in profound and sometimes surprising ways. We explore how these control nodes are layered to form complex and dynamic circuits, discuss their role in disease, and conclude by outlining opportunities for future study of post-transcriptional regulation in macrophages.

CD8 T cell activation and acquisition of cytolytic activity, which is essential for adaptive immunity, begins with priming in the lymph node (LN). Jobin et al. recently identified a second, delayed priming phase driven by competition with regulatory T cells for IL-2, revealing a rate-limiting step with significant clinical implications.

Neutrophil numbers fluctuate over time, peaking during active phases to enhance immunity. The molecular link between circadian signals and cellular clocks remains unclear. Yi Du et al. show that light-regulated Per2 increases reactive oxygen species (ROS) production and bacterial killing in zebrafish neutrophils by controlling Hmgb1 expression, highlighting the impact of light on immune function.

Multiomics advances have led to breakthroughs in understanding human early life immunity. Adaptive memory immune cells have been detected in fetal tissue extremely early in gestation, where they may respond to maternal exposures. These promising findings lay the groundwork for future research on the lifelong impact of early immune development.