Researchers Discover How Body Regulates Most Abundant Type Of White Blood Cell

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Researchers Discover How Body Regulates Most Abundant Type Of White

Blood Cell

Every day, the human body manufactures and destroys about 100 billion

neutrophils- the most common type of white blood cell and one of the

most highly-produced cells. Neutrophils live about eight hours, are

bacteria-eaters and are a key component of the immune system. Without

them, the body can be subject to life-threatening infection.

But how does the body keep the number of neutrophils produced constant

in the blood, a mystery to scientists for decades? Researchers at the

Cardiovascular Research Center at the University of Virginia Health

System believe they have the answer.

They’ve discovered that these bacteria-killers in the blood are

regulated by a sophisticated physiological process, much like the

body’s blood pressure or water level. Their research is detailed in the

March 23 issue of the journal Immunity.

Working with laboratory mice, Dr. Klaus Ley, professor of biomedical

engineering at U.Va. and a U.Va. graduate student, Stark,

discovered a new type of T lymphocyte, the cells that are the main

means of providing the body with immune capability. This newly

discovered cell, found in the lymph nodes of the gut, is called a Tn

cell by Ley and Stark because it is responsible for regulating

neutrophils.

“As far as we know, these primitive cells make mainly one cytokine, the

protein produced primarily by white blood cells. This cytokine is

IL-17,” Ley explained. “These cells are also under the control of

another cytokine, IL-23. As the name suggests, these cells are

responsible for regulating neutrophil numbers produced in the bone

marrow. This finding will probably have significant impact not only for

research, but also for clinical medicine.”

Ley said the discovery could lead to new therapies to treat

neutropenia- a lack of neutrophil production that can lead to bad

infections in cancer patients who undergo chemotherapy, radiation or a

bone marrow transplant. The research could also be useful in treating

inflammatory and autoimmune diseases, like rheumatoid arthritis or

lupus, where neutrophil production may be part of the problem.

“Currently, neutropenia is treated with a drug called GCSF,” Ley

explained. “But it may be more beneficial in the long-run to develop

drugs targeting the IL-17 cytokine.”

Ley and Stark call the process they’ve discovered the neutrophil

turnstile.

“We found negative feedback,” Stark explained. “Neutrophils watch and

wait for bacteria. When they find bacterial production in the gut, the

body will make a cytokinethat drives neutrophil production.”

But when neutrophils die, Stark and Ley explained, they get absorbed up

by other cells called macrophages and dendritic cells, downregulating

their production of IL-23. That way the body can actually ‘sense’ how

many neutrophils have gotten to where they need to go in the body.

Stark and Ley theorize that this ‘turnstile’ is likely located in the

mesenteric lymph node in the middle of the gut, and possibly the lungs

and skin.

Co-authors on the Immunity paper with Ley and Stark are Yuqing Huo,

L. Burcin, Margaret A. and S. Olson. The research

was supported by grants from the National Institutes of Health. The

researchers also received invaluable assistance from U.Va.’s Flow

Cytometry Core Facility.

http://www.sciencedaily.com/releases/2005/03/050322134117.htm

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