First evidence that the brain’s native dendritic cells can muster an immune response

Jan 22, 2010
Protecting the brain. New experiments show a special population of the immune system’s sentinels, dendritic cells (green), at work in the brain. Brain dendritic cells gather around the border of stroke-damaged brain tissue and also stimulate T cells (red) to fight off infections.

( -- Since their initial discovery in 1973, dendritic cells, the sentinels of the immune system, have turned up in a number of places other than the immune organs. They stand guard in the heart, for instance, and in 2008, the first population native to the brain was identified. New research shows that dendritic cells are not only present in the brain, but active, too. They confront foreign substances and seem to form a barrier between healthy and stricken brain tissue following a stroke.

The is a delicate organ, robustly defended. A thick skull shields it from any direct exposure to the outside world, and the blood-brain barrier keeps out any foreign substances that are circulating within. New research shows that the brain may have its own specialized immune defenses, too.

In 2008, researchers at Rockefeller University first identified a population of dendritic cells, the sentinels of the immune system, that was native to the brain. Now they have shown that these cells are not likely sleeping on the job. In experiments published recently in and Brain Behavior and Immunity, the researchers show that these brain dendritic cells can muster the immune system’s soldier T cells when confronted by certain threats. They also show that, unlike dendritic cells from elsewhere in the body, brain dendritic cells line up along the periphery of stroke-damaged , perhaps as a barricade protecting the healthy cells outside.

“We knew they were there and now we know they are immunologically functional,” says Karen Bulloch, director of Rockefeller’s Neuroimmunology and Inflammation Program, which was funded by the Peter Deane Trust following the initial discovery of brain dendritic cells. Bulloch is a research associate professor who works with Bruce S. McEwen’s Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology and the Laboratory of Cellular Physiology and Immunology headed by Ralph M. Steinman, who discovered dendritic cells in 1973.

Dendritic cells capture and process foreign substances called antigens before presenting them to T cells, which multiply and attack the invaders. To test their activity in the brain, the researchers, led by Rockefeller graduate Andres Gottfried-Blackmore, now a student at Weill Cornell Medical College, injected a mouse brain with interferon-γ, an immune-response molecule produced during specific inflammatory responses. They found that the interferon increased the number of brain dendritic cells without recruiting dendritic cells from elsewhere in the . They then exposed the dendritic cells to a model antigen called OVA, prompting a proliferation of OVA-specific . The brain dendritic cells also proved far more effective at stimulating T cell proliferation in the same test than similar immune-related cells called microglia, which reside in the brain in huge numbers. The difference suggests a specialized role for brain dendritic cells.

In other experiments, led by postdoctoral fellow Jennifer Felger and in collaboration with the laboratory of Costatino Iadecola at Weill Cornell, researchers studied the response of brain dendritic cells labeled with a fluorescent protein after inducing strokes in mice. Unlike dendritic cells from elsewhere in the body, which were drawn into the stroke-damaged tissues, brain dendritic cells closed ranks around the perimeter of the damage, forming a barrier between stricken and healthy tissues.

Brain remain largely mysterious, but their immune-related activity suggests they play an important part in protecting the brain. The researchers are also interested in finding out what they do when they are not battling threats such as strokes or infections. “It is equally important to understand what they do when they are not defending the brain,” Bulloch says.

Explore further: Mutant protein in muscle linked to neuromuscular disorder

More information:

-- Proceedings of the National Academy of Sciences 106, 20918-20923 (December 8, 2009). Acute in vivo exposure to interferon-γ enables resident brain dendritic cells to become effective antigen presenting cells, Andres Gottfried-Blackmore, Ulrike W. Kaunzner, Juliana Idoyaga, Judit C. Felger, Bruce S. McEwen and Karen Bulloch

-- Brain, Behavior and Immunity online: November 13, 2009. Brain dendritic cells in ischemic stroke: Time course, activation state, and origin. Jennifer C. Felger, Takato Abe, Ulrike W. Kaunzner, Andres Gottfried-Blackmore, Judit Gal-Toth, Bruce S. McEwen, Costantino Iadecola and Karen Bulloch

add to favorites email to friend print save as pdf

Related Stories

First evidence of native dendritic cells in brain

May 15, 2008

In a finding that has the potential to change the way researchers think about the brain, scientists at Rockefeller University have found dendritic cells where they’ve never been seen before: among this organ’s ...

Dendritic cells as a new player in arteries and heart valves

Feb 17, 2009

( -- In 1973, Ralph M. Steinman launched a new scientific discipline when he published his discovery of the dendritic cell, an odd-shaped player in the immune system. Since then, dendritic cells have proved to ...

Dendritic cells stimulate cancer-cell growth

Nov 17, 2006

Since their discovery at Rockefeller University some 30 years ago, dendritic cells have been recognized as key players on the immune-system team, presenting antigens to other immune cells to help them respond to novel insults. ...

Immune cells reveal fancy footwork

Dec 01, 2008

Our immune system plays an essential role in protecting us from diseases, but how does it do this exactly? Dutch biologist Suzanne van Helden discovered that before dendritic cells move to the lymph nodes they lose their ...

'Super' enzyme may lead way to better tumor vaccines

Dec 04, 2006

A "super" form of the enzyme Akt1 could provide the key to boosting the effect of tumor vaccines by extending the lives of dendritic cells, the immune-system master switches that promote the response of T-cells, which attack ...

To spread, skin cancer attacks immune dendritic cells

May 27, 2009

( -- Dendritic cells are the sentinels of the immune system. When they’re alert and on guard, they will marshal the body’s immunosoldiers, T cells, to battle at the sight of harmful pathogens. But some diseases, ...

Recommended for you

Proper stem cell function requires hydrogen sulfide

1 hour ago

Stem cells in bone marrow need to produce hydrogen sulfide in order to properly multiply and form bone tissue, according to a new study from the Center for Craniofacial Molecular Biology at the Herman Ostrow School of Dentistry ...

Bionic ankle 'emulates nature'

6 hours ago

These days, Hugh Herr, an associate professor of media arts and sciences at MIT, gets about 100 emails daily from people across the world interested in his bionic limbs.

Firm targets 3D printing synthetic tissues, organs

8 hours ago

(Medical Xpress)—A University of Oxford spin-out, OxSyBio, will develop 3D printing techniques to produce tissue-like synthetic materials for wound healing and drug delivery. In the longer term the company ...

User comments : 0

More news stories

Turning off depression in the brain

Scientists have traced vulnerability to depression-like behaviors in mice to out-of-balance electrical activity inside neurons of the brain's reward circuit and experimentally reversed it – but there's ...

Spate of Mideast virus infections raises concerns

A recent spate of infections from a frequently deadly Middle East virus is raising new worries about efforts to contain the illness, with infectious disease experts urging greater vigilance in combatting ...

Clean air: Fewer sources for self-cleaning

Up to now, HONO, also known as nitrous acid, was considered one of the most important sources of hydroxyl radicals (OH), which are regarded as the detergent of the atmosphere, allowing the air to clean itself. ...

Thinnest feasible nano-membrane produced

A new nano-membrane made out of the 'super material' graphene is extremely light and breathable. Not only can this open the door to a new generation of functional waterproof clothing, but also to ultra-rapid filtration. The ...

There's something ancient in the icebox

Glaciers are commonly thought to work like a belt sander. As they move over the land they scrape off everything—vegetation, soil, and even the top layer of bedrock. So scientists were greatly surprised ...