Trends in Immunology最新文献

Recent discoveries reveal that inflammasome signaling in neurons extends beyond host defense to influence fundamental aspects of brain function, including synaptic plasticity, axon remodeling, and exosome-mediated intercellular communication. This review explores how basal neuronal inflammasome activity contributes to central nervous system (CNS) homeostasis and how heightened signaling in neurons drives neuroinflammatory and degenerative processes. Understanding these dual roles of neuronal inflammasomes provides new insights into neuroimmune crosstalk and identifies potential targets for modulating repair and inflammation in CNS injury and disease.

The developmental origins of health and diseases concept posits that early-life exposure to environmental adversities increases risks for diverse noncommunicable and infectious diseases. Among these adversities, maternal malnutrition is a critical determinant of offspring health trajectories. Maternal malnutrition from preconception to lactation can durably alter cellular and tissue function in the offspring. We propose that tissue-resident macrophages (TRMs) act as central mediators of this developmental programming. Seeding tissues during embryogenesis, integrating metabolic and hormonal signals, and persisting throughout life, TRMs can encode maternal nutritional states into lasting tissue adaptations. We summarize how specific maternal diets program distinct TRM subsets and how programmed TRMs link maternal nutritional statuses to disease susceptibility. TRMs may offer early intervention targets to improve offspring health.

The intestinal epithelium functions as an immune-metabolic interface, integrating environmental signals to maintain systemic homeostasis. Intraepithelial lymphocytes (IELs), interspersed within the epithelial layer, form a highly interactive network with intestinal epithelial cells (IECs) to coordinate barrier defense, immune tolerance, and metabolic regulation. IECs orchestrate IEL development, positioning, and functional programming. Reciprocally, IELs modulate epithelial physiology, nutrient uptake, and epithelial repair. Dysregulation of the IEL-IEC unit contributes to intestinal and extraintestinal pathologies. This review discusses current advances in IEL-IEC bidirectional communication, highlighting the influences of diet, microbial metabolites, and immune checkpoints on this interface. We propose a paradigm in which the IEL-IEC interplay functions as a key immunometabolic regulatory unit and represents a promising therapeutic target for systemic diseases.

The SARS-CoV-2 pandemic has drawn global attention to post-acute infection syndromes (PAIS), with millions affected by post-acute sequelae of COVID-19 (PASC, or Long COVID). While Long COVID is newly defined, PAIS have been described for over a century following epidemic infections. Multiple pathogens - including influenza, Epstein-Barr virus, and Borrelia burgdorferi, among others - can precipitate persistent, poorly understood symptoms. Chronic illnesses such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have long been linked to infectious triggers. This recurring association highlights critical knowledge gaps and underscores the need for systematic investigation. Unlike prior pandemics, the current era offers advanced technologies and analytic tools to address these gaps. Defining the biology of Long COVID may yield broader insights into host-pathogen interactions and mechanisms of chronic illness.

Identification of antigenic ligands for the γδ T cell receptor (TCR) has remained a highly challenging goal since the emergence in the 1980s of γδ T cells as a distinct immune compartment. In a significant advance more than 12 years ago, endothelial protein C receptor (EPCR), a cell-surface-expressed major histocompatibility complex (MHC)-like protein that binds phospholipids, was identified as the first ligand for a human γδ TCR to be validated by direct binding experiments: a finding that undoubtedly posed more questions than it answered. In this review we discuss how features of this single clonotypic specificity anticipated insights into adaptive-like human γδ T cell biology that emerged in subsequent investigations, and we highlight recent findings about EPCR that point towards the relevance of such responses in anti-pathogen and potentially anti-tumour immunity.

Advances in single-cell sequencing have transformed our understanding of immune aging by enabling high-resolution dissection of age-associated changes in cellular composition and function. Recent years have seen a surge in studies leveraging single-cell multi-omics to chart immune trajectories across the human lifespan, uncovering previously unrecognized heterogeneity and functional shifts in peripheral immune cells. While these technologies offer unprecedented insights, they also pose significant technical and analytical challenges, including data integration across platforms and populations. In this review, we critically examine landmark studies, compare emerging immune aging clocks, and highlight opportunities for clinical translation. By decoding immune aging at single-cell resolution, we move closer to early detection of immunosenescence, personalized immunomodulation, and precision strategies to extend healthspan in aging populations.

Natural killer (NK) cells protect from viral infection, cancer, and metastasis, and are emerging as valuable therapeutics for cancer treatment. NK-cell control of viral infection has been studied intensively, but less is known in the context of cancer. Multiple associative, preclinical, and early phase clinical studies have revealed the ability of NK-cell-based therapies to contribute to cancer control. Development of effective NK-cell therapeutics will be facilitated by a deeper understanding of the mechanisms controlling NK cell function across an array of cancer types and states. This review will focus on recent studies of the transcription factors that control NK cell function and their response to leukemia, solid tumors, and metastasis.

Burn et al. reveal a previously unrecognised, non-catalytic function of myeloperoxidase (MPO) in neutrophil extracellular trap (NET) formation; integrating super-resolution microscopy and biochemical approaches, they demonstrated that MPO's oligomeric state governs chromatin decondensation, redefining MPO as a structural chromatin modifier with implications for diseases driven by dysregulated NETosis.

Sepsis, a life-threatening condition triggered by infection, disrupts the body's immune balance and remains a major global health challenge. This forum explores the dual roles of cytokines in sepsis: their overactivation drives 'cytokine storms,' and dysregulation leads to immunosuppression. It also discusses regulatory mechanisms for developing targeted therapies.

This essay uses immunology to illuminate human relationships. Moving beyond self/non-self toward danger-based models, it draws parallels between cytokine communication and language, tolerance and forgiveness, microbiota diversity and coexistence. Recognizing these metaphors reveals pathways toward healthier connections within individuals, communities, and societies.