Langerhans cell histiocytosis reveals a new IL-17A–dependent pathway of dendritic cell fusion
Autor: | Aymeric Rivollier, Nicola E. Annels, Chantal Rabourdin-Combe, Fabienne Coury, Jacques Tebib, Maurizio Aricò, Christine Delprat, Maria Brytting, Sophia Djebali, Selma Olsson, Alessandra Santoro, Carole Speziani, Jan-Inge Henter, Olga Azocar, R. Maarten Egeler, Monique Flacher |
---|---|
Rok vydání: | 2007 |
Předmět: |
biology
business.industry medicine.medical_treatment Neurodegeneration General Medicine Dendritic cell medicine.disease General Biochemistry Genetics and Molecular Biology Bone resorption Histiocytosis Cytokine Langerhans cell histiocytosis RANKL Giant cell Immunology medicine biology.protein business |
Zdroj: | Nature Medicine. 14:81-87 |
ISSN: | 1546-170X 1078-8956 |
Popis: | IL-17A is a T cell-specific cytokine that is involved in chronic inflammations, such as Mycobacterium infection, Crohn's disease, rheumatoid arthritis and multiple sclerosis. Mouse models have explained the molecular basis of IL-17A production and have shown that IL-17A has a positive effect not only on granuloma formation and neurodegeneration through unknown mechanisms, but also on bone resorption through Receptor activator of NF-kappaB ligand (RANKL) induction in osteoblasts. Langerhans cell histiocytosis (LCH) is a rare disease of unknown etiology, lacking an animal model, that cumulates symptoms that are found separately in various IL-17A-related diseases, such as aggressive chronic granuloma formation, bone resorption and soft tissue lesions with occasional neurodegeneration. We examined IL-17A in the context of LCH and found that there were high serum levels of IL-17A during active LCH and unexpected IL-17A synthesis by dendritic cells (DCs), the major cell type in LCH lesions. We also found an IL-17A-dependent pathway for DC fusion, which was highly potentiated by IFN-gamma and led to giant cells expressing three major tissue-destructive enzymes: tartrate resistant acidic phosphatase and matrix metalloproteinases 9 and 12. IFN-gamma expression has been previously documented in LCH and observed in IL-17A-related diseases. Notably, serum IL-17A-dependent fusion activity correlates with LCH activity. Thus, IL-17A and IL-17A-stimulated DCs represent targets that may have clinical value in the treatment of LCH and other IL-17A-related inflammatory disorders. |
Databáze: | OpenAIRE |
Externí odkaz: |