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Whence White Blood Cells?

Bone marrow supplies white blood cells to every organ in the body. But researchers now suggest that skin might have an edge: It can produce certain types of immune cells on its own, relying on reinforcements from the bone marrow only in times of trouble.

As the first line of defense against infection, the skin encounters constant attacks. To fend them off, it relies on immune cells called dendritic cells, which detect invaders and then call in the cavalry of T cells to attack. Skin-specific dendritic cells called Langerhans cells originate in the bone marrow, but how they get to the skin, and how they maintain their numbers, had never been explained.

To determine whether Langerhans cells replenish by dividing in the skin or by recruiting replacements from the bloodstream, pathologist Miriam Merad of Stanford University and colleagues surgically joined two mice so that they shared a blood supply. The mice differed by only one gene, allowing the researchers to determine which mouse contributed which cells. Within 10 days, several types of white blood cells were completely mixed, but even after 6 months, each mouse contained only its own Langerhans cells, the team reports online 4 November in Nature Immunology. Therefore, they conclude, stem cells in the skin, rather than cells delivered through the bloodstream, normally replenish Langerhans cells. However, when the team damaged mice's skin with ultraviolet light, the traumatized skin summoned precursor cells circulating in the bloodstream to replace the Langerhans cells.

Why doesn't the skin usually recruit dendritic cells like other organs? It could be because the ranks of Langerhans cells in the skin don't need replacing very often, says dermatologist Stephen Katz, director of the National Institute of Arthritis and Musculoskeletal and Skin Diseases in Bethesda, Maryland. "The controversy is how quickly [Langerhans cells] are turning over," he says. "These are very long-lived cells."

If researchers can understand how Langerhans cells regenerate, they may be able to grow them in the lab, Merad says. That could help recipients of bone marrow transplants. In some cases, the transplanted marrow launches an immune attack against the host's cells, a potentially lethal condition called graft-versus-host disease. Particular targets of the attack include the skin, liver, and gut, where Langerhans cells congregate. Replacing the host's Langerhans cells with cells from the donor, Merad says, might stave off the disease.

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Katz's Web site