Pair of Molecular Regulators Maintains Normal Eosinophil Levels

An international team of cell biologists have identified the mechanism that regulates production of eosinophils by the blood marrow, which may lead to development of drugs to control diseases caused by an excess of these cells.

Eosinophils are immune cells responsible for combating certain infections such as multicellular parasites. Along with mast cells, they also control mechanisms associated with allergy and asthma. Eosinophils develop in the bone marrow under the control of the central eosinophil growth factor interleukin 5 (IL-5) before migrating into the blood. In normal individuals, eosinophils make up about 1%–6% of white blood cells, and are about 12–17 micrometers in size. Under normal conditions, eosinophils are found in the medulla and the junction between the cortex and medulla of the thymus and in the lower gastrointestinal tract, ovary, uterus, spleen, and lymph nodes but not in the lung, skin, or esophagus. The presence of eosinophils in these latter organs is associated with disease.

Investigators at Tel Aviv University (Israel) and Cincinnati Children's Hospital Medical Center (Ohio, USA) searched for the molecular signals that regulate eosinophil production.

They reported in the November 10, 2013, online edition of the journal Nature Immunology that IL-5 activity in eosinophils was regulated by the paired immunoglobulin-like receptors PIR-A and PIR-B. PIR-A countered the activity of IL-5 and triggered eosinophil apoptosis. However, in eosinophilia the activity of PIR-A was blocked by overexpression of PIR-B, and the eosinophils did not die.

Experiments using a model system of asthmatic mice that lacked PIR-B showed that these animals had little expansion of eosinophils in their blood and lungs and less asthmatic inflammation in their lungs than normal mice. The lack of PIR-B prevented eosinophils from reaching harmful levels.

"The fundamental knowledge we have gained may one day yield new therapies to treat devastating eosinophilic disorders," said senior author Dr. Ariel Munitz, senior lecturer in microbiology and clinical immunology at Tel Aviv University.

Researchers are now seeking drugs to either enhance the toxic effect of PIR-A on eosinophils or to weaken PIR-B activity in order to reduce its inhibitory effect on PIR-A.

Related Links:
Tel Aviv University
Cincinnati Children's Hospital Medical Center