A novel small molecule compound possesses immunomodulatory properties on bone marrow-derived dendritic cells via TLR7 signaling pathway and alleviates the development of SLE

- FC-99 inhibits the expression of CD40 induced by R848.
- FC-99 inhibits inflammation by suppressing NF-κB signaling pathway.
- FC-99 ameliorates the lupus like syndrome of MRLlpr/lpr mice.
- FC-99 modulates the percentage and the activation of mDCs in vivo.

Dendritic cells (DCs) play an important role in the development and maintenance of immune tolerance. Activation of TLR7, which is expressed in DCs, is thought to contribute to the complex pathophysiology of systemic lupus erythematosus (SLE). In this study, we analyzed the in vitro and in vivo function of a novel small-molecule compound, FC-99, which was previously reported to have immunomodulatory functions. We found that FC-99 inhibited the expression of CD40 and inflammatory mediators (IL-6, IL-12, and CXCL-10), as well as R848-induced phosphorylation of IκB-α. We also present evidence that FC-99 is remarkably efficacious in the treatment of murine lupus. Interestingly, FC-99 affected the maturation and percentage of DCs in lupus-prone mice. Therefore, FC-99 may serve as a potential drug candidate for treatment of SLE.