IFN-γ 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-γ-dependent cell survival and host resistance. Irgm1 regulates the expansion/survival of mature effector CD4+ T lymphocytes by protecting them from IFN-γ-induced autophagic cell death. Importantly, mice deficient in both IFN-γ 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-γ responses by protecting these cells from autophagy-dependent cell death.
CG Feng, L Zheng, D Jankovic, A Báfica, JL Cannons, WT Watford, D Chaussabel, S Hieny, P Caspar, PL Schwartzberg, MJ Lenardo, A Sher. The immunity-related GTPase Irgm1 promotes the expansion of activated CD4+ T cell populations by preventing interferon-gamma-induced cell death. Nat Immunol 2008; 9: 1279- 87.
PMID: 18806793 DOI: 10.1038/ni.1653