Immunological Reviews最新文献

Epilepsy is a brain disorder characterized by recurrent seizures, which are brief episodes of abnormal electrical activity in the brain and involuntary movement that can lead to physical injury and loss of consciousness. Seizures are canonically accompanied by increased inflammatory cytokine production that promotes neuroinflammation, brain pathology, and seizure propagation. Understanding the source of pro-inflammatory cytokines which promote seizure pathogenesis could be a gateway to precision epilepsy drug design. This review discusses the inflammasome in epilepsy including its role in seizure propagation and negative impacts on brain health. The inflammasome is a multiprotein complex that coordinates IL-1β and IL-18 production in response to tissue damage, cellular stress, and infection. Clinical evidence for inflammasome signaling in epileptogenesis is reviewed followed by a discussion of emerging strategies to modulate inflammasome activity in epilepsy.

Environmental insults during early development heavily affect brain trajectories. Among these, maternal infections, high-fat diet regimens, and sleep disturbances pose a significant risk for neurodevelopmental derangements in the offspring. Notably, scattered evidence is starting to emerge that also paternal lifestyle habits may impact the offspring development. Given their key role in controlling neurogenesis, synaptogenesis and shaping neuronal circuits, microglia represent the most likely suspects of mediating the detrimental effects of prenatal insults. For some of these environmental triggers, like maternal infections, ample literature evidence demonstrates the central role of microglia, also delineating the specific transcriptomic and proteomic profiles induced by these insults. In other contexts, the analysis of microglia is still in its infancy. Fostering these studies is needed to define microglia as potential therapeutic target in the frame of disorders consequent to maternal immune activation.

Myelin is the membrane surrounding neuronal axons in the central nervous system (CNS), produced by oligodendrocytes to provide insulation for electrical impulse conduction and trophic/metabolic support. CNS dysfunction occurs following poor development of myelin in infancy, myelin damage in neurological diseases, and impaired regeneration of myelin with disease progression in aging. The lack of approved therapies aimed at supporting myelin health highlights the critical need to identify the cellular and molecular influences on oligodendrocytes. CNS macrophages have been shown to influence the development, maintenance, damage and regeneration of myelin, revealing critical interactions with oligodendrocyte lineage cells. CNS macrophages are comprised of distinct populations, including CNS-resident microglia and cells associated with CNS border regions (the meninges, vasculature, and choroid plexus), in addition to macrophages derived from monocytes infiltrating from the blood. Importantly, the distinct contribution of these macrophage populations to oligodendrocyte lineage responses and myelin health are only just beginning to be uncovered, with the advent of new tools to specifically identify, track, and target macrophage subsets. Here, we summarize the current state of knowledge on the roles of CNS macrophages in myelin health, and recent developments in distinguishing the roles of macrophage populations in development, homeostasis, and disease.

Aicardi-Goutières syndrome (AGS) is a progressive genetic encephalopathy caused by pathogenic mutations in genes controlling cellular anti-viral responses and nucleic acid metabolism. The mutations initiate autoinflammatory processes in the brain and systemically that are triggered by chronic overproduction of type I interferon (IFN), including IFN-alpha. Emerging disease-directed therapies aim to dampen autoinflammation and block cellular responses to IFN production, creating an urgent and unmet need to understand better which cells, compartments, and mechanisms underlying disease pathogenesis. In this review, we highlight existing pre-clinical models of AGS and our current understanding of how causative genetic mutations promote disease in AGS, to promote new model development and a continued focus on improving and directing future therapies.

Alzheimer's disease (AD) is the most common neurodegenerative disorder and cause of dementia. Despite the prevalence of AD, there is a lack of effective disease modifying therapies. Recent evidence indicates that the gut microbiome (GMB) may play a role in AD through its regulation of innate and adaptive immunity. Gut microbes regulate physiology through their production of metabolites and byproducts. Microbial metabolites may be beneficial or detrimental to the pathogenesis and progression of inflammatory diseases. A better understanding of the role GMB-derived metabolites play in AD may lead to the development of therapeutic strategies for AD. In this review, we summarize the function of bioactive GMB-derived metabolites and byproducts and their roles in AD models. We also call for more focus on this area in the gut–brain axis field in order to create effective therapies for AD.

This manuscript sheds light on the impact of maternal breast milk antibodies on infant health. Milk antibodies prepare and protect the newborn against environmental exposure, guide and regulate the offspring's immune system, and promote transgenerational adaptation of the immune system to its environment. While the transfer of IgG across the placenta ceases at birth, milk antibodies are continuously replenished by the maternal immune system. They reflect the mother's real-time adaptation to the environment to which the infant is exposed. They cover the infant's upper respiratory and digestive mucosa and are perfectly positioned to control responses to environmental antigens and might also reach their circulation. Maternal antibodies in breast milk play a key role in the immune defense of the developing child, with a major impact on infectious disease susceptibility in both HIC and LMIC. They also influence the development of another major health burden in children—allergies. Finally, emerging evidence shows that milk antibodies also actively shape immune development. Much of this is likely to be mediated by their effect on the seeding, composition and function of the microbiota, but not only. Further understanding of the bridge that maternal antibodies provide between the child and its environment should enable the best interventions to promote healthy development.