OBJECTIVE: Tofacitinib, which is a Janus kinase (JAK) inhibitor, has shown 
clinical effects in the treatment of rheumatoid arthritis. JAKs are important 
kinases in lymphocyte differentiation; however, their function in dendritic 
cells (DCs) is unknown. In this study, the function of JAKs in DCs was 
investigated with tofacitinib.
METHODS: The effects of tofacitinib on the maturation of human monocyte-derived 
DCs induced by lipopolysaccharide (LPS) stimulation were investigated. In 
addition, its effects on T cell stimulatory capability was investigated by 
coculturing with naïve CD45RA-positive T cells.
RESULTS: Tofacitinib decreased expression of CD80/CD86 in a 
concentration-dependent manner in LPS-stimulated DCs; however, it did not affect 
HLA-DR expression. Tofacitinib suppressed tumour necrosis factor, interleukin 
(IL)-6 and IL-1β production without affecting transforming growth factor (TGF)-β 
and IL-10 production. Meanwhile, CD80/CD86 expression in DCs was enhanced by 
type I interferon (IFN) stimulation, and the LPS-induced CD80/CD86 expression 
was inhibited by an antibody to type I IFN receptor. Furthermore, tofacitinib 
suppressed production of type I IFN and activation of interferon regulatory 
factor (IRF)-7, which is a transcription factor involved in CD80/CD86 and type I 
IFN expression. Tofacitinib also decreased the T cell stimulatory capability of 
DCs and increased expression of indoleamine 2,3-dioxygenase (IDO)-1 and IDO-2.
CONCLUSIONS: Tofacitinib, a JAK1/JAK3 inhibitor, affected the activities of 
human DCs. It decreased CD80/CD86 expression and T cell stimulatory capability 
through suppression of type I IFN signalling. These results suggest a novel mode 
of action for tofacitinib and a pivotal role for JAKs in the differentiation of 
DCs.