Various cytokines are reported to play a role in SLE and represent an attractive target for therapy with many monoclonal antibodies and small molecular inhibitors already developed to target cytokines and their signalling pathways. We recently identified genetic variants in 5% of SLE patients that reduce the function of an inhibitor of cytokine signalling, SH2B3. These variants increase cell responsiveness to cytokines and promote immune dysregulation. This also promotes the survival of autoreactive B cells. We have opportunities for specific projects that investigate the role of particular cytokines and cellular mechanisms in promoting escape of these autoreactive B cells.