Immunological Reviews最新文献

Sex plays a key role in shaping both anti-cancer immunity and autoimmunity. Biological factors underlying sexual dimorphism have now been identified in multiple aspects of anti-cancer immunity and autoimmunity. These factors include sex differences in hormone levels, chromosome complement, and expression of the long non-coding RNA XIST. In this review, we discuss recent advances delineating how these differences alter immune responses against cancer and autoimmune responses against healthy tissues. Moreover, we now understand that hormone levels change (e.g., in mini-puberty, menopause, and andropause) and that somatic alterations in chromosomal complement accumulate (e.g., loss of Y [LOY] chromosome) across the lifespan. We also include here a discussion of how these changes affect anti-cancer immunity and autoimmunity across a lifetime. These recent advances will set the stage for identifying immunotherapeutic approaches that optimize anti-cancer immunity while controlling the autoimmune responses.

There are sex differences with immune responses where females exhibit stronger immune responses compared to males. Both sex hormones and sex chromosome differences between males and females contribute to the observed sex differences with innate and adaptive immune cell composition and function. Here, we present recent findings investigating sex differences with immune cells and responses, highlighting contributions from sex hormones or X-linked genes. We also review the epigenetic gene regulatory mechanisms that form the inactive X chromosome (Xi), known as X-Chromosome Inactivation (XCI), the heterochromatic nature of the Xi that allows for selective gene reactivation, and recent work investigating the mechanisms of XCI maintenance in female immune cells. We also highlight some dosage-sensitive X-linked genes involved in female-biased autoimmune disease, discuss sex differences with immune signaling pathways, and sex differences with viral infections and vaccine responses with the ultimate goal to leverage these insights for the development of sex-specific therapeutic interventions for immune-related diseases.

Arterial walls of large- and intermediate-sized arteries consist of three layers, that is, the intima, the media, and the adventitia. Under physiological conditions, the intima mainly comprises endothelial cells and a few monocyte/macrophages and dendritic cells; the media consists of smooth muscle cells and elastic fibers; and the adventitia is a complex connective tissue with structures as diverse as scattered immune cells, small blood vessels, lymph vessels, and multiple components of the nervous system. This review focuses on a subtype of tertiary lymphoid structures termed artery tertiary lymphoid organs (ATLOs), which develop specifically in atherosclerotic arterial segments in the adventitia but not in normal arteries. ATLOs have been characterized in aging hyperlipidemic mice and later have been identified in various diseased segments of the arterial tree, including the carotid arteries, the coronary arteries, and the aorta in humans. The effects of ATLOs on atherosclerosis remain largely unknown. Indeed, ATLOs host pro-inflammatory and anti-inflammatory immune cell subtypes. Stage-III ATLOs contain activated B cell follicles in which germinal centers develop in apparent antigen-dependent B cell maturation cycles. Recent research supports the idea that ATLOs create neuroimmune cardiovascular interfaces (NICIs), which may serve as key hubs in which three tissues interact: the nervous system, the immune system, and the cardiovascular system. Recent evidence indicates that NICIs are capable of impacting disease progression. These interfaces connect atherosclerotic plaques to the immune system, produce disease-related autoantibodies, participate in the development of autoreactive T cells, and transmit signals from arteries to the brain and receive signals from the brain in hardwired polysynaptic axonal connections.

Epidemiological studies consistently show that many parasitic diseases affect males more frequently than females. These disparities are multifactorial, arising partly from gender-specific behaviors that influence exposure risk and health-seeking practices, especially in low- and middle-income countries. Increasing evidence also highlights that biological sex differences within the immune system significantly shape susceptibility to and control of parasitic infections. Recent advances combining classical immunology with single-cell transcriptomics have revealed hormonal and chromosomal factors driving sex-specific differences in innate and adaptive immune cells. These differences can critically influence the course and outcome of parasitic diseases. However, many studies on parasitic diseases still lack adequately sex-disaggregated data or fail to apply state-of-the-art immunological analyses needed to fully characterize biological sex effects. Studies in rodent models that mirror the sex bias observed in humans provide valuable tools to analyze immune mechanisms at the cellular level and dissect underlying biological differences. In this review, we summarize current knowledge on sex differences in key cellular components of innate and adaptive immunity and discuss their relevance for selected parasitic diseases of major global importance—leishmaniasis, Chagas disease, amebiasis, schistosomiasis, and malaria.

Aging is the most important yet unmodifiable risk factor for cardiovascular disease (CVD). As a result, targeting cardiovascular aging has emerged as a promising strategy to promote long-term cardiovascular health. This review summarizes current knowledge on the effects of aging within the cardiovascular system as well as systemic processes that modulate them. We highlight the roles of cellular senescence and the senescence-associated secretory phenotype (SASP), emphasizing their heterogeneous contributions to chronic low-grade inflammation and tissue remodeling—collectively termed inflammaging. Advances in biomarkers, animal models, and systems biology approaches have deepened our understanding of the interplay between senescence, inflammaging, and cardiovascular dysfunction, including the pivotal role of macrophages in senescent cell clearance. Therapeutic strategies are diverse, ranging from senolytic approaches designed to selectively eliminate senescent cells, to SASP modulation, and interventions targeting chronic inflammation and metabolic dysregulation. Of particular interest, drugs already in clinical use—such as metformin and other anti-diabetic agents—show beneficial effects on aging-related pathways, suggesting that their cardiovascular protection may in part reflect anti-aging properties. Despite these advances, therapies directly targeting senescence and inflammaging to reduce the global burden of CVD remain an urgent unmet need.

Inflammation is increasingly recognized as a central driver of heart failure (HF), particularly in older adults, yet the underlying immune mechanisms remain diverse and incompletely understood. Clonal hematopoiesis (CH), defined by the expansion of somatically mutated hematopoietic clones, has emerged as a risk factor for the development of numerous age-related diseases including HF. Experimental and clinical evidence suggests that mutant clones carrying driver gene mutations promote a pro-inflammatory immune cell phenotype that contributes to cardiac injury, remodeling and adverse outcomes. Notably, CH has been implicated in HF across diverse etiologies, including both HFrEF and HFpEF, highlighting its broad impact on a vast array of HF syndromes. More recently, it has been discovered that hematopoietic loss of the Y chromosome (LOY) also contributes to HF. LOY appears to shift macrophages toward a fibrotic and away from a pro-inflammatory phenotype, contrasting with that observed for driver gene mutations and suggesting that different somatic alterations contribute to HF via divergent mechanisms. In this review, we examine the clinical and experimental associations between CH and HF. We also explore how CH may drive age-related immune heterogeneity in HF and highlight its potential to be leveraged for personalized interventions in patients with HF.