Mac-1+ myelopoiesis induced by CFA: a clue to the paradoxical effects of IFN-γ in autoimmune disease models

The mechanisms accounting for the protective role of endogenous interferon γ (IFN-γ) in certain murine autoimmune disease models, versus a disease-promoting role in others, have remained elusive. The protective effect of IFN-γ might be unique to models that rely on the use of complete Freundʹs adjuvant (CFA) and whose pathogenesis is predominantly driven by delayed-type hypersensitivity. In these models, IFN-γ counteracts disease development by inhibiting CFA-induced proliferation of a pathogenically important Mac-1+ cell population(s). This calls into question our usual conceptualization of the balance between innate and specific immunity in these models, as well as their clinical relevance, particularly when the role of IFN-γ or related cytokines is considered