Tofacitinib is a novel Janus kinase (JAK) inhibitor approved for the treatment of rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis. In clinical trials, the most common adverse events observed were nasopharyngitis, upper respiratory tract infections, and zoster. JAKs are found downstream of the type II cytokine receptor family used by a number of T
We treated primary human keratinocytes and synoviocytes with tofacitinib and subsequently added various cytokines and bacterial surface proteins before evaluation of the response via RT-qPCR. CD69 expression on tofacitinib-treated PBMCs was investigated via flow cytometry.
We found a markedly reduced gene expression of all tested antiviral peptides such as MX1 or ISG15 in keratinocytes and synoviocytes in the presence of tofacitinib in vitro. Additionally, we found that JAK inhibition reduced activation of T cells after stimulation with bacterial LPS or viral VZV gE.
The antiviral immunity is strongly inhibited in the presence of tofacitinib in vitro, while the antimicrobial immunity does not seem to be affected. In T cells, the overall activation process seems to be influenced by tofacitinib. These findings suggest that tofacitinib has an impact on antiviral immunity such as patients treated with tofacitinib often show adverse events like herpes zoster.