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.
Feng
Carl G
CG
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-8003, USA. cfeng@niaid.nih.gov
Zheng
Lixin
L
Lenardo
Michael J
MJ
Sher
Alan
A
D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002470:Cell Survival / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007109:Immunity / Q000187:drug effects*; D007371:Interferon-gamma / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D008954:Models, Biological
C096000:Ifi1 protein, mouse; D007371:Interferon-gamma; D019204:GTP-Binding Proteins