Immature dendritic cells in multiple myeloma are prone to osteoclast‐like differentiation through interleukin‐17A stimulation

Summary Interleukin 17A (IL17 A ), a cytokine involved in allergy, inflammation and osteoclastogenesis, was investigated in multiple myeloma ( MM ) to assess its role in the osteoclast ( OC )‐like activity of marrow immature dendritic cells ( iDC s). Comparing nine MM patients with control subjects affected by monoclonal gammopathy of undetermined significance, we found high IL 17A expression in the marrow plasma of MM patients in parallel with its deposits within the stromal matrix. Increased expression of the IL 17A receptor ( IL 17RA) was also found in primary myeloma iDC s, which underwent OC ‐like transdifferentiation after IL 17A stimulation. To assess the role of IL 17A, we measured the activity of the IL 17/ IL 17 RA pathway in IL 17A‐transdifferentiated iDC s and the expression of functional OC genes by W estern blotting and real‐time polymerase chain reaction. These cells showed increased RNA transcription of genes enrolled in the maturation of OC s, while NFATC 1 and FOS were induced by IL 17A, independently of NFKB 1 phosphorylation. Moreover, the concurrent phosphorylation of the L ip isoform of CEBPB and the down‐regulation of MAFB supported the activation of IL 17 RA pathway in OC ‐like transdifferentiated iDC s that was apparently unrelated to TNFRSF 11A signalling. These data emphasize the involvement of iDC s in MM hyperactive osteoclastogenesis and suggest that their bone resorption activity is also regulated, at least in vitro , by IL 17RA.