Interferon gamma in autoimmunity: A complicated player on a complex stage

•Reviews interferon gamma's functional capacities.•Highlights pro- and anti-inflammatory actions of interferon gamma and how ongoing disease processes impact functional outcome.•Discusses evidence regarding the contributions of interferon gamma to specific autoimmune settings.

Early views of autoimmune disease cast IFNγ as a prototypic pro-inflammatory factor. It is now clear that IFNγ is capable of both pro- and anti-inflammatory activities with the functional outcome dependent on the physiological and pathological setting examined. Here, the major immune modulatory activities of IFNγ are reviewed and current evidence for the impact of IFNγ on pathology and regulation of several autoimmune diseases and disease models is summarized.