Research defines dendritic cell lineage

Mar 19, 2009

(PhysOrg.com) -- Dendritic cells were discovered more than 30 years ago, but their pedigree has never been fully charted. They were known to be key immune system cells born in bone marrow, but their adolescence remained a mystery, their path to infection-fighting adulthood confused. Now, in experiments published in Science, researchers at The Rockefeller University have identified these special cells’ rites of passage: They have shown the developmental point when dendritic cells part ways with closely related immune cells known as monocytes, at least in mice. The findings could have important implications for research on dendritic cell-based vaccines all over the world.

“So far, people in clinics are trying to make vaccines — cancer vaccines and others — based on dendritic without fully taking into account the different types,” says Michel C. Nussenzweig, head of the Laboratory of Molecular Immunology, where the research was conducted. “The different types have different biological properties. Defining how they arise is important in terms of being able to target individual types, which could be very significant for vaccine development.”

Prior research had shown that two kinds of dendritic cells, dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs), as well as have a common ancestor cell in . Kang Liu, a postdoctoral associate in Nussenzweig’s lab, led the genealogical research into where the lines diverged, a question that has sparked controversy ever since dendritic cells were discovered. She focused the investigation on cDCs, which are expected to be more useful for vaccine development than the monocytes commonly used now.


Awkward adolescents. Three hours after being introduced in a mouse, precursors for classical spleen dendritic cells (pre-cDCs, green) attach to blood vessels near where (blue) and (red), other important players in the immune system, are active. New research has solved the long-standing problem of how to differentiate pre-cDCs from other dendritic cells and their cousins, monocytes.

Liu had a hunch about how an adolescent classical spleen dendritic cell might look. She deduced that it would express one cell receptor common to all known dendritic cells, Flt3, but would lack a certain protein that enables the grown-up cell to capture bacteria or viruses and present them to other immune cells for destruction. She developed markers for these theoretical dendritic adolescents and found them in bone marrow, blood and lymph organs such as the spleen and lymph node, which filter bodily fluids. She named these cells preclassical spleen dendritic cells (pre-cDCs), and found that wherever they were from, they grew into adult dendritic cells in mice within days.

Using a two-photon microscope and other biochemical tests, Liu and her collaborators Gabriel Victora and Tanja Schwickert were able to trace the life cycle of cDCs from their original ancestor to their transformation into fully committed pre-cDCs in the bone marrow, their migration in the blood and growth into full-fledged cDCs dancing around the lymph system. The pre-cDCs they injected grew up to behave just like the native cDCs in mice. Liu also unveiled the related but distinct lineages of plasmacytoid dendritic cells and monocytes.

“We identified the migrating dendritic cell precursor and really took it as a tool to understand the differentiation of dendritic cells from head to toe, from the early stage in bone marrow to the late stage development and regulation in the lymph organ,” Liu said.

The discovery of the dendritic cell precursor could have important applications in immunotherapy. Many immunotherapies today are based on monocytes, which can be chemically prodded to develop dendritic cell-like characteristics but are not the genuine article.

More information: Science online: March 12, 2009. In Vivo Analysis of Dendritic Cell Development and Homeostasis. Kang Liu, Gabriel D. Victora, Tanja A. Schwickert, Pierre Guermonprez, Matthew M. Meredith, Kaihui Yao, Fei-Fan Chu, Gwendalyn J. Randolph, Alexander Y. Rudensky and Michel Nussenzweig

Provided by Rockefeller University (news : web)

Explore further: US scientists make embryonic stem cells from adult skin

add to favorites email to friend print save as pdf

Related Stories

New origin found for a critical immune response

Mar 01, 2009

An immune system response that is critical to the first stages of fighting off viruses and harmful bacteria comes from an entirely different direction than most scientists had thought, according to a finding by researchers ...

Dendritic cells as a new player in arteries and heart valves

Feb 17, 2009

(PhysOrg.com) -- 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 ...

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 ...

'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 ...

Recommended for you

Leeches help save woman's ear after pit bull mauling

Apr 18, 2014

(HealthDay)—A pit bull attack in July 2013 left a 19-year-old woman with her left ear ripped from her head, leaving an open wound. After preserving the ear, the surgical team started with a reconnection ...

New pain relief targets discovered

Apr 17, 2014

Scientists have identified new pain relief targets that could be used to provide relief from chemotherapy-induced pain. BBSRC-funded researchers at King's College London made the discovery when researching ...

User comments : 0

More news stories

Filipino tests negative for Middle East virus

A Filipino nurse who tested positive for the Middle East virus has been found free of infection in a subsequent examination after he returned home, Philippine health officials said Saturday.

Study says we're over the hill at 24

(Medical Xpress)—It's a hard pill to swallow, but if you're over 24 years of age you've already reached your peak in terms of your cognitive motor performance, according to a new Simon Fraser University study.

NASA's space station Robonaut finally getting legs

Robonaut, the first out-of-this-world humanoid, is finally getting its space legs. For three years, Robonaut has had to manage from the waist up. This new pair of legs means the experimental robot—now stuck ...

Ex-Apple chief plans mobile phone for India

Former Apple chief executive John Sculley, whose marketing skills helped bring the personal computer to desktops worldwide, says he plans to launch a mobile phone in India to exploit its still largely untapped ...

Egypt archaeologists find ancient writer's tomb

Egypt's minister of antiquities says a team of Spanish archaeologists has discovered two tombs in the southern part of the country, one of them belonging to a writer and containing a trove of artifacts including reed pens ...

Airbnb rental site raises $450 mn

Online lodging listings website Airbnb inked a $450 million funding deal with investors led by TPG, a source close to the matter said Friday.