**6. Conclusion**

In summary, SphKs and S1P/S1PR signalling appear to play essential roles in modulating RA pathogenesis. The SphK1 pathway is activated and likely plays a pro-inflammatory role in mouse models of inflammatory arthritis. It is fascinating that the blockade of SphK1 activity results in the simultaneous reduction of several inflammatory responses such as pro-inflammatory cytokines and inflammatory cell infiltration into the synovium. Excessive S1P and enhanced S1P receptor expression are detected in the synovium of RA patients. S1P and signalling through S1P receptors induce expression of inflammatory cytokines and suppress apoptosis of B lymphoblastoid cells and fibroblast-like synoviocytes. Although the possible mechanism by which S1P exerts its activity in RA remains to be fully characterized, further understanding of S1P metabolism and S1P receptor expression by synovial tissues represents an exploitable objective for the development of novel chemotherapeutic agents in the treatment of RA.
