The temporal integration of opposing cytokine signals important in differentiation fate decisions for IFN-γ classical activation versus IL-4 activation and other alternate macrophage activation pathways, and the spectrum of cell populations occurring in between, is a multi-faceted, highly nuanced immune mechanism that underpins the development of chronic inflammation and autoimmunity and leads to acute clinical relapses. The gene discussed is IL4; the disease is Autoimmunity.