Treatment of rheumatoid arthritis (RA) has developed dramatically by the 
appearance of biologics. However the development of a new anti-rheumatic drug is 
necessary because of its issue on route of administration and expense. Recently, 
inhibitors targeting tyrosine kinase known as Janus kinase (Jak) has shown 
prominent effect on RA. Jak family is comprised by Jak1, Jak2, Jak3 and Tyk2 
which is necessary for signal transduction for inflammatory cytokines. INCB18424 
targeting Jak1/2 and CP690,550 targeting Jak3 has been developed and is now on 
phase II clinical study for RA. Results from those clinical studies have proven 
that these inhibitors can be effective as biologics with few side effects. 
However, it has been reported that inhibitors are less specific than it has been 
expect and that non-specificity can be important for its effect. Therefore, we 
think that the mechanism of inhibitors cannot be explained by its inhibition of 
a single kinase. Herein, we describe IL-10 overproduction by Jak3 and Stat6 
deficient dendritic cell. We speculate that this is one possible mechanism of 
action for CP690,550 although as for its non-specificity we need further 
investigation to predict not only its effect but also its side effect in a long 
term administration.