Given that PGE2 is the main product of COX-2 signaling and COX-2/PGE2 pathway is one of the pivotal signals responsible for the immunosuppressive effects of MSCs, our results suggest that direct inhibition of NLRP3 inflammasome can be one of the core strategies of hUCB-MSCs immunomodulation to attenuate excessive inflammatory responses, particularly in RA microenvironment. Here, NLRP3 is linked to rheumatoid arthritis.