Background: IL-17A, IL-22 and TNF- α play leading roles in Psoriatic arthritis (PsA) but their regulatory role on JAK-STAT signaling for pannus formation remains unknown. Objectives: To address whether the key regulatory cytokines of PsA induce phosphorylation of STAT3 and can JAK-STAT inhibitor antagonize effects on pannus formation induced by TNF- α, IL-17 and IL-22. Methods: We tested the effect of tofacitinib on the IL-6, IL-8 and MMP-3 production in FLS. FLS were cultured with TNF-α, IL-17A or IL-22 and ELISAs were performed for IL-6, IL-8 and MMP-3. MTT assay was done for proliferation and immunoblot studies of FLS lysates were done for STAT3. Results: IL-17, IL-22, TNF-α induced phosphorylation of STAT3. PsA FLS pre-treated with tofacitinib showed decreased levels of phospho-STAT3 compared to the FLS cells without tofacitinib. IL-17, TNF-α and IL-22 induced significant proliferation of PsA and RA FLS. PsA and RA FLS stimulated with IL-17A, IL-22 or TNF-α produced significantly more IL-6 IL-8 and MMP-3 compared to media and that could be reduced when these FLS were pre-treated with tofacitinib. Conclusion: FLS proliferation, IL-6, IL-8 and MMP-3 production by FLS are the two critical events of pannus formation induced by IL-17A, TNF-α and IL-22 and is regulated by the JAK-STAT kinase system. These data support a role for JAK-STAT signaling pathways in PsA and provides mechanisms of actions of tofacitinib for its efficacy.