Neuroimmunology

Nature Reviews Immunology has launched a special Series on Neuroimmunology. We hope the articles in this Series serve as guiding lights on what promises to be an exciting scientific journey.

Microglia are increasingly implicated in the maintenance and regeneration of myelin, which is damaged with normal ageing and in several neurodegenerative diseases. This article reviews the mechanisms by which microglia support and restore myelin health and the factors that influence these crucial microglial functions.

This Review explores the complex roles of immune cells in the onset and progression of multiple sclerosis, describing the influence of environmental and genetic factors on immune cell phenotype and function. The authors highlight that teasing out the precise roles of different immune cell subsets at different stages of the disease will be key to effective treatment strategies.

This Review from Tansey and colleagues explores how an ageing immune system, host genetics and exposure to various environmental stressors combine to promote the development of Parkinson disease.

Although B cells represent only a minor cell population in the central nervous system (CNS), they can contribute to CNS pathology — most notably in multiple sclerosis — through antibody and effector molecule secretion and antigen presentation. Here, Jain and Yong discuss the roles of B cells in the CNS and examine the potential for targeting these cells in various neurological conditions.

In this Review, Manabe and Heneka examine how the systemic inflammation associated with sepsis can lead to acute cerebral dysfunction known as sepsis-associated encephalopathy (SAE). Moreover, they suggest that some of the mechanisms involved in SAE may be relevant for understanding the cognitive impairments that develop in some patients with COVID-19.

Beth Stevens and Matthew Johnson discuss the unexpected finding that classical complement components guide synaptic pruning in the brain and are necessary for healthy brain function.

Here, Harald Prüss discusses how autoantibodies can contribute to neurological diseases. The identification of specific autoantibodies to neuronal and glial targets has increased our understanding of autoimmunity in the central nervous system and led to the reclassification of some diseases previously thought to result from infection or ‘idiopathic’ causes.

In this Review, Kipnis and colleagues explain how signals from the immune system can shape host behavioural responses, even in the absence of infection or disease. In particular, the authors focus on the cytokine pathways that modulate behavioural responses and consider the evolutionary basis of these neuroimmune interactions.

In this Review, Zengeler and Lukens consider how innate immune signalling pathways contribute to healthy brain development and the implications for neurodevelopmental disorders.

This Review by Harschnitz and Studer explains how human pluripotent stem cell technology can be used to explore antiviral immunity in the central nervous system. Such technology could help us to identify new therapies for a range of central nervous system viral infections and to uncover the mechanisms behind the central nervous system complications associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.

In this Review, Rolls and colleagues discuss regulation of immune responses by the nervous system. The authors focus on the benefits of neuronal regulation of immunity, the mechanisms involved and the brain areas involved in neuro-immune crosstalk.

Immune cells and neural cells interact in numerous tissues and organs and can have local and far-reaching physiological effects. Understanding these intimate bidirectional interactions is providing insight into the gut–brain axis, as well as the maternal gut–fetal brain axis.

This Review considers the link between pain and the immune system. Nociceptors are directly activated by immune mediators and microbial products and, in turn, release neuropeptides that shape immune responses. These neuroimmune pathways can contribute to protective immunity from infections but also lead to chronic pain.

By sensing environmental, dietary, microbial and metabolic cues, the ligand-activated transcription factor aryl hydrocarbon receptor controls complex transcriptional programmes that are relevant to autoimmune, neoplastic, metabolic and degenerative diseases.

In this Review, Shi and Holtzman highlight our growing understanding of the innate immune mechanisms that contribute to Alzheimer disease with a specific focus on microglial cells, apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2).

This Review describes recent advances in our understanding of the ontogeny, development and function of brain-resident macrophages and microglia, including their normal functions during brain development and homeostasis and how disturbance of these functions may precipitate neurodegenerative and neuropsychiatric diseases.

This Review focuses on the protective and pathological roles of different T cell subsets in the central nervous system (CNS). The authors explain how effector, memory and regulatory T cell populations are primed and recruited to the CNS, and discuss the plasticity of these populations, particularly in the context of viral infection and autoimmunity.

This Review discusses the contribution of different cytokine networks to inflammation in the central nervous system (CNS). In neuroinflammatory diseases such as multiple sclerosis, CNS-invading leukocytes produce many of the cytokines that are associated with disease. By contrast, in Alzheimer disease and other neurodegenerative diseases, tissue-resident cells are the main source of pathological cytokines.

In this Review, the authors relate the growing appreciation of the neuroimmune circuits that link inflammatory and immune responses with depressive behaviours. They explore the evolutionary basis of this neuroimmune link and discuss how a better understanding of these pathways may lead to new therapies that treat depression by targeting the immune system.

This Review provides an insightful discussion on the current concepts in multiple sclerosis research, including genetic predisposition and environmental triggers, and explores the evolving link between inflammation and neurodegeneration. The authors highlight the clinical challenges and key questions that remain to be addressed.