The immunobiology of MIF: function, genetics and prospects for precision medicine

The role of macrophage migration inhibitory factor (MIF) in autoimmunity is underscored by data showing that common functional polymorphisms in MIF are associated with disease susceptibility or clinical severity. MIF can regulate glucocorticoid-mediated immunosuppression and has a prominent function in cell survival signalling. Further specific functions of MIF are now being defined in different autoimmune diseases and MIF-targeted biologic therapeutics are in early-stage clinical trials. The unique structure of MIF is also directing the development of small-molecule MIF antagonists. Together, these efforts could provide a means of selectively intervening in pathogenesis and overcoming MIF-related genetic susceptibility to many rheumatic diseases. The pleiotropic cytokine macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of autoimmune inflammatory disorders. This Review discusses MIF biology and signalling, its mechanisms of action and its involvement in rheumatic diseases, including opportunities for targeted therapies.