Langerhans cell histiocytosis reveals a new IL-17A–dependent pathway of dendritic cell fusion
Author: ["Fabienne Coury","Nicola Annels","Aymeric Rivollier","Selma Olsson","Alessandra Santoro","Carole Speziani","Olga Azocar","Monique Flacher","Sophia Djebali","Jacques Tebib","Maria Brytting","R Maarten Egeler","Chantal Rabourdin-Combe","Jan-Inge Henter","Maurizio Arico","Christine Delprat"]
Publication: Nature Medicine
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Abstract
IL-17A is a T cell–specific cytokine1 that is involved in chronic inflammations, such as Mycobacterium infection2, Crohn's disease3, rheumatoid arthritis4 and multiple sclerosis5. Mouse models have explained the molecular basis of IL-17A production6,7 and have shown that IL-17A has a positive effect not only on granuloma formation8 and neurodegeneration9 through unknown mechanisms, but also on bone resorption through Receptor activator of NF-κB ligand (RANKL) induction in osteoblasts4,10. 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 neurodegeneration11,12. 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-γ and led to giant cells expressing three major tissue-destructive enzymes: tartrate resistant acidic phosphatase and matrix metalloproteinases 9 and 12. IFN-γ expression has been previously documented in LCH13 and observed in IL-17A–related diseases14,15,16,17. 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.
Cite this article
Coury, F., Annels, N., Rivollier, A. et al. Langerhans cell histiocytosis reveals a new IL-17A–dependent pathway of dendritic cell fusion. Nat Med 14, 81–87 (2008). https://doi.org/10.1038/nm1694
