Grants Awarded

Mechanisms of IL-17A-Dependent Dendritic Cell Long-Term Survival and Fusion in Langerhans Cell Histiocytosis

Principal Investigator
Christine Delprat MD, PhD
INSERM – Lyon, France

Date of Award
December 2007

Amount of Award
Total amount paid by the Histiocytosis Association of Canada

Layperson Summary
Langerhans cell histiocytosis (LCH) may affect any age group, from the newborn to the elderly, but clinical features, pathogenesis, and treatment outcome derives from the pediatric experience. The incidence for LCH of around 1:200,000 children per year, peaks at 1–3 years.

LCH is an ‘orphan’ disease that belongs to the Histiocytoses. The course of LCH is often unpredictable, varying from spontaneous regression and resolution to rapid progression and death or repeated recurrence and recrudescence with a considerable risk of permanent sequelae since tumors destroy the tissue where they grow: bone in 80% of patients with multisystem disease, but also soft tissues and occasionally central nervous system involvement.

We have just demonstrated that inside lesions, dendritic cells (DC) and multinucleated giant cells (MGC) produce IL-17A, a messenger of the human immune system which has a dominant role in the development and maintenance of several chronic inflammations, such as Mycobacterium infection, Crohn’s disease, rheumatoid arthritis and multiple sclerosis. Thus, LCH belongs to IL-17A-related disease family. Moreover, we have just discovered a novel IL-17A-dependent pathway of DC fusion which probably gives rise to MGC observed in LCH lesions.

Our objective is to discover the mechanisms of DC long-term survival induced by IL-17A and required for DC fusion in order to design therapeutic agents able to prevent DC survival and their subsequent fusion and differentiation into aggressive tissue-destructive MGC. These therapeutic agents may abrogate or at least reduce tissue destruction in all LCH lesions.