Several cytokines signalling via Janus Kinase (JAK) proteins have been 
implicated in the pathogenesis of immune-mediated inflammatory diseases, 
including psoriasis and rheumatoid arthritis (RA). Tofacitinib, a small JAK 
inhibitor, is approved for the treatment of RA and has demonstrated good 
efficacy in psoriasis phase III clinical trials. In this work, we analysed the 
in vitro effects of tofacitinib on the functions of human dendritic cells (DCs) 
and macrophages. When assessing the effects of tofacitinib on monocyte-derived 
DCs, we observed reduced differentiation of monocytes into immature DCs, as 
evidenced by a decreased transcription of CD209 and CD80. Phenotype assessment 
in the presence of tofacitinib suggested a switch towards a M1-like macrophage 
phenotype, as evidenced by the expression of M1 markers such as iNOS, as well as 
cytokines typically expressed by M1 cells, including IL-12 and IL-23. Of note, 
Arginase1 and CD200R, typically expressed by M2 cells, were absent on 
tofacitinib-treated DCs. Furthermore, tofacitinib affected the response of 
differentiated DCs to maturation stimuli such as LPS and IFNγ, resulting in a 
partial up-regulation of IL-23 and down-regulation of IL-12, as assessed by 
qPCR. When investigating macrophage development, we found that tofacitinib 
inhibited the ability of monocytes to differentiate and polarize into regulatory 
M2 macrophages, while rather enhancing the ability to develop into inflammatory 
M1-like macrophages, as evidenced by decreased expression of the M2 marker 
CD200R and enhanced production of IL-12 and IL-23. In conclusion, tofacitinib 
impacts the differentiation of human DCs and macrophages, it particularly 
favours generation of M1-like pro-inflammatory macrophages.