Trends in Immunology最新文献

The complement genes harbour genetic variants that affect numerous diseases; however, these genes are notoriously repeat-heavy, and these repeat regions are largely unexplored for disease-relevant genetic variation. Elucidating these 'dark' regions is now possible using long-read sequencing (LRS), enabling identification of novel disease-relevant genetic variants.

Recently, a large pool of antigens derived from viral and bacterial microorganisms showing molecular mimicry with tumour-cell-expressed antigens was identified. These antigens can be presented by MHC molecules and elicit T cells that are crossreactive with microbial antigens and tumour-cell-associated antigens. In the setting of metastatic melanoma, such T cells can contribute to the response induced by immune checkpoint blockade therapy. Here, the current understanding of molecular mimicry in T cell-mediated tumour immunity and how this might be exploited for developing new preventive and therapeutic approaches for cancer is described. In particular, the literature on the concept and evidence of molecular mimicry in cancer is reviewed, covering the whole translational spectrum, from the antigen discovery strategy to the clinical evaluation.

Intrahepatic immune responses are often insufficient to control hepatitis virus infections. A recent study by Venzin and colleagues demonstrates a detailed mechanism by which an intrahepatic tricellular network and the cytokine IL-27 can augment virus-specific immunity.

Gut dysbiosis and intestinal inflammation may contribute to neurological disorders through the gut-brain axis. A recent report by White et al. uncovered that intestinal inflammation triggers the migration of microbiota-specific CD4⁺ T cells to the brain, where they drive neuroinflammatory responses via IL-23R/GM-CSF.

Maternal immune activation (MIA), triggered by infection or inflammation during pregnancy, is a well-recognized risk factor for neurodevelopmental disorders (NDDs) such as autism spectrum disorder (ASD). Clinical cohort studies and rodent models suggest that natural killer (NK) cells play a significant role in NDD pathogenesis, but the underlying mechanisms remain poorly defined. Here, we summarize the key immune mediators involved in MIA-induced NDDs, emphasizing microglia as a central hub. We then examine emerging evidence implicating aberrant NK cell activation in ASD, underscoring their overlooked contribution to impaired neurodevelopment. Finally, we discuss potential mechanisms of NK cell-microglia crosstalk in NDDs. Elucidating these interactions in the context of MIA will be crucial for developing preventive and therapeutic strategies against inflammation-driven NDDs.

The evolution of the fetal immune system within the womb is a delicate balancing act: it is trained to not reject maternal antigens, while equipping itself with 'learned' immunity to survive and thrive in the outside world. In this opinion article, we propose that a deliberate maternal touch via immune and nutritional influences, orchestrated, in part, by microbiota-derived components, imprints the fetal immune system with the needed immune memory and epigenetic marks to navigate a far less nurturing outside world, including early microbial colonizers in the newborn's intestine, pathogens and irritants, and allergens in food. We redefine the hygiene hypothesis to include prenatal maternal microbial exposures, priming fetal immune development for long-term fitness and reduced inflammatory/autoimmune disease risk.

Neutrophil extracellular trap (NET) formation, or NETosis, is a key innate immune response that contributes to cardiovascular diseases, including vascular inflammation, atherosclerosis, and thrombosis. In the cardiovascular system, neutrophils encounter mechanical cues such as shear stress, matrix stiffness, and cyclic stretch that influence their activation and NET release. This review examines emerging evidence linking altered mechanotransduction to dysregulated NETosis in vascular aging and cardiovascular pathology. We also highlight intracellular signalling pathways by which neutrophils sense and respond to mechanical stress. Understanding how biomechanical cues regulate NETosis may uncover novel therapeutic opportunities to control inflammation in cardiovascular disease without compromising host defence.

T cells can exchange parts of their plasma membrane along with membrane-associated proteins through trogocytosis. During trogocytosis only certain subsets of membrane-associated proteins seem to be exchanged suggesting a fine-tuned mechanism regulating the selection of what can be transferred. In this review, we describe potential models of trogocytosis and discuss mechanisms that could regulate this process in T cells. Additionally, we delve into how exchanged proteins polarize on the surface of recipient cells, discuss how trogocytosis allows T cells to acquire new functions, and summarize ways to modulate this process in T cells. Understanding trogocytosis can help us better understand the immune response and develop more effective immunotherapies.

Interactions between autoimmune disorders and lymphoid malignancies have long been recognized; for instance, with prominent autoimmune manifestations in B- and T-cell lymphomas and an increased risk of lymphoma development in individuals with autoimmune diseases. More recently, several lines of evidence have shown that these two disease types have shared origins, defined by common genetic lesions and pathogenic cell states. Recent work suggests that the safeguards that protect normal lymphocyte development and adaptive immunity against the development of autoimmune diseases and lymphoid malignancies are based on similar sensing mechanisms of pathological lymphocytes. Here, we propose that mechanisms of negative selection that are designed to eliminate autoreactive lymphocytes also operate in suppressing the development of lymphoid malignancies.

Tumor-associated macrophages (TAMs) are key regulators of the tumor microenvironment (TME), but their heterogeneity, driven by tumor-derived cues, poses challenges for therapeutic targeting and underscores the need for precise macrophage reprogramming strategies. Through a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR) screen, Marelli et al. identified chemosensors as lipid-sensing regulators of macrophage activity, revealing new therapeutic avenues.