Trends in Immunology最新文献

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.

The advancement of immunotherapy faces significant challenges, including extending its benefits to a growing number of patients and enhancing its efficacy across different tumor types. In this context, γδ T cells emerge as particularly promising candidates owing to their distinctive biological features such as MHC-independent activation, potent cytotoxicity, and capacity to bridge innate and adaptive immunity. Recently, advanced single-cell techniques have allowed detailed γδ T cell characterization in the tumor microenvironment (TME) and have emphasized their heterogeneity, mechanisms of activation, and response to immune checkpoint blockade (ICB). This review provides a comprehensive summary of recent advances in understanding γδ T cells in colorectal cancer (CRC), with a particular emphasis on their prognostic and therapeutic relevance in both primary tumors and metastatic disease.

Intestinal homeostasis is crucial for overall health, and its maintenance relies on a complex and delicate interplay between intestinal epithelial cells, the gut microbiota, and the immune system. Among immune components, group 3 innate lymphoid cells (ILC3s), which primarily reside in the intestinal microenvironment, play a crucial role in maintaining gut homeostasis. Through the expression of multiple effector molecules such as interleukin (IL)-22 and major histocompatibility complex class II (MHCII), ILC3s orchestrate intestinal epithelial responses and regulate innate and adaptive immunity, thereby collectively promoting a symbiotic host-microbiota relationship, supporting immune tolerance, and providing protection against pathogens. This review summarizes current understanding of ILC3 functions in gut homeostasis, highlights their interactions with the microbiota and other cell types, and outlines how aberrant ILC3 activity contributes to disease pathogenesis.

Pregnancy requires dynamic immune adaptations that balance tolerance, homeostasis, and defense at the maternal-fetal interface. Recent advances integrating findings from human placental samples with those from refined animal models now enable a detailed analysis of how cellular responses in mid and late gestation contribute to major obstetrical complications - with distinct clinical manifestations - such as preterm birth, fetal growth restriction, and pre-eclampsia. In this Opinion article we propose a unifying paradigm: the breakdown of maternal-fetal immune homeostasis. We highlight regulatory T cells and decidual macrophages as complementary regulators of antigen-specific tolerance and nonspecific homeostasis, whereas effector T cell infiltration in chronic placental inflammation and neutrophil-driven inflammation in acute chorioamnionitis exemplify pathological immune activation. Together, these examples illustrate how immune programs that sustain mid-to-late pregnancy, when dysregulated, drive pathology and open new therapeutic opportunities.

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.

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.