Interferon-inducible immunity-related GTPase Irgm1 regulates IFN gamma-dependent host defense, lymphocyte survival and autophagy.

IFN gamma is a pleiotropic cytokine that plays a key role in host resistance, yet when not properly regulated can become detrimental to the host. The interferon-inducible Immunity Related GTPase family M member 1 (Irgm1), previously characterized as an effector molecule required for macrophage microbicidal activity, has been shown recently to control IFN gamma-dependent cell survival and host resistance. Irgm1 regulates the expansion/survival of mature effector CD4(+) T lymphocytes by protecting them from IFN gamma-induced autophagic cell death. Importantly, mice deficient in both IFN gamma and Irgm1 were rescued from the lymphocyte depletion and increased mortality that typically occurs in Irgm1(-/-) animals following pathogen exposure. We propose that Irgm1 plays a major role in maintaining T lymphocyte homeostasis during host IFN gamma responses by protecting these cells from autophagy-dependent cell death.