Grants Awarded

Principal Investigator and Co-Investigator
Barrett J. Rollins MD, PhD (PI); Barbara Brandner PhD; Gayane Badalian MD, PhD
Dana-Farber Cancer Institute, Harvard Medical School
Boston, Massachusetts USA

Date of Award
December 2007

Amount of Award
$50,000

Layperson Summary
Langerhans cell histiocytosis (LCH) is a rare disease that mainly affects children. Cells of the immune system, called Langerhans cells (LCs), accumulate in various organs and cause damage, in severe cases even leading to death. The cause of this disease and the factors leading to its progression are still unknown.

Chemokine receptors act as signposts on cells of the immune system. In healthy people the chemokine receptor CCR6 is involved in retaining resting LCs in the skin while the chemokine receptor CCR7 directs mature LCs to the lymph nodes, but they never appear at the same time on the same cells. However, in LCH both of these receptors are present on abnormal LCs. The simultaneous appearance of these receptors is probably not the cause for the disease, but could be responsible for the misguided accumulation of LCH cells in different organs. We want to test the importance of this finding in mice by genetically modifying their LCs to display these two chemokine receptors simultaneously.  We will examine the journey of these cells in the genetically modified mice and we will compare it to mice that do not display these receptors on their LCs. We will examine organs in these mice such as skin, lymph nodes, spleen, liver, brain and bone for the presence of LCs and other cells that are found in human patients suffering from LCH and contribute to the organ damage. In addition, we will investigate the migration of LCs after mild inflammatory skin challenge and we also will study the isolated LCs outside of the mouse.

Our mouse model of abnormal LC migration will help us understand the progression of LCH and other histiocytic disorders and give insight into disease mechanisms. Many pharmaceutical companies are developing drugs that block chemokine receptors. If our work shows that these receptors contribute to the manifestations of LCH, then we can plan to test the effects of chemokine receptor blockers in patients with the disease.