The nervous and immune systems are in constant dialogue, but details of how these two essential systems are integrated and functionally cooperate at the molecular level are only now being revealed. Much of the recent research in this area has focused on the role of immune cells and immune mediators in the initiation and progression of specific neurological diseases, such as multiple sclerosis and Alzheimer's disease. But how do autoimmune T cells get into the brain and how do they contribute to neurological diseases? Is microglial cell activation in the brain neurodestructive or neuroprotective? Can serum antibodies affect brain function? What are the functional contributions of genetic determinants to multiple sclerosis susceptibility? These and other questions have important implications for the treatment of neurological disorders with an inflammatory component.

This Focus issue brings together Review and Opinion articles that describe our current understanding of the crosstalk between the nervous and immune systems and of the immunopathogenesis of and emergent immunotherapies for specific neurological disorders. All of the articles in this Focus are available free to registered users until 20 June 2009.


From the editors

doi:10.1038/nri2585

Nature Reviews Immunology 9, 385 (2009)

Research Highlights

Neuroimmunology: Finding a way into the brain

Elaine Bell

doi:10.1038/nri2549

Nature Reviews Immunology 9, 386 (2009)

In the news: Cladribine hope for multiple sclerosis

Kirsty Minton

doi:10.1038/nri2579

Nature Reviews Immunology 9, 387 (2009)

In Brief

doi:10.1038/nri2583

Nature Reviews Immunology 9, 388 (2009)

In Brief

doi:10.1038/nri2584

Nature Reviews Immunology 9, 389 (2009)

Autoimmunity: A new target in multiple sclerosis?

Rachel David

doi:10.1038/nri2574

Nature Reviews Immunology 9, 390-391 (2009)

Neuroimmunology: Basement membrane laminins guard the CNS

Kirsty Minton

doi:10.1038/nri2576

Nature Reviews Immunology 9, 391 (2009)

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Reviews

Autoimmune T cell responses in the central nervous system

Joan Goverman

doi:10.1038/nri2550

Nature Reviews Immunology 9, 393-407 (2009)

Our understanding of the role of T cells in the induction of autoimmune disease in the central nervous system has progressed rapidly in recent years. Here, Joan Goverman provides us with a comprehensive overview of this field and discusses the controversies that remain.

From genes to function: the next challenge to understanding multiple sclerosis

Lars Fugger, Manuel A. Friese & John I. Bell

doi:10.1038/nri2554

Nature Reviews Immunology 9, 408-417 (2009)

With recent studies revealing the genetic determinants of multiple sclerosis, our attention must now turn to defining the function of the candidate genes in disease pathogenesis. This Review describes our progress so far and the approaches required to tease out the contribution made by multiple genetic and environmental factors.

Reflex control of immunity

Kevin J. Tracey

doi:10.1038/nri2566

Nature Reviews Immunology 9, 418-428 (2009)

Work in the past decade has revealed the role of neural circuits in modulating inflammatory conditions. Here, Kevin Tracey discusses the inflammatory reflex, and in particular the efferent arc of this reflex, which is known as the cholinergic anti-inflammatory pathway. In this pathway, acetylcholine activity suppresses the release of pro-inflammatory cytokines.

Regulation of innate immune responses in the brain

Serge Rivest

doi:10.1038/nri2565

Nature Reviews Immunology 9, 429-439 (2009)

In this Review article, Serge Rivest discusses how microglial cells (the resident innate immune cells of the central nervous system) are activated during infection and injury, whether microglial cell activation is neurodestructive or neuroprotective, and how targeting these cells could be a therapeutic approach for the treatment of Alzheimer's disease.

A molecular trio in relapse and remission in multiple sclerosis

Lawrence Steinman

doi:10.1038/nri2548

Nature Reviews Immunology 9, 440-447 (2009)

The relapsing-remitting form of multiple sclerosis affects around two thirds of patients with this disease. This Review discusses the roles of three key molecules — alpha4beta1 integrin, its binding partner osteopontin and the chaperone protein alphaB crystallin — in the biology of relapse and remission.

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Perspectives

Losing your nerves? Maybe it's the antibodies

Betty Diamond, Patricio T. Huerta, Paola Mina-Osorio, Czeslawa Kowal & Bruce T. Volpe

doi:10.1038/nri2529

Nature Reviews Immunology 9, 449-456 (2009)

In this Opinion article, Betty Diamond and colleagues propose that common serum antibodies that crossreact with brain antigens might be responsible for many acquired changes or congenital impairments in cognition and behaviour in the absence of overt brain inflammation.

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