RRC ID 19384
Author Oura R, Arakaki R, Yamada A, Kudo Y, Tanaka E, Hayashi Y, Ishimaru N.
Title Induction of rapid T cell death and phagocytic activity by Fas-deficient lpr macrophages.
Journal J Immunol
Abstract Peripheral T cells are maintained by the apoptosis of activated T cells through the Fas-Fas ligand system. Although it is well known that normal T cells fail to survive in the Fas-deficient immune condition, the molecular mechanism for the phenomenon has yet to be elucidated. In this study, we demonstrate that rapid cell death and clearance of normal T cells were induced by Fas-deficient lpr macrophages. Transfer of normal T cells into lpr mice revealed that Fas expression on donor T cells was promptly enhanced through the IFN-γ/IFN-γR. In addition, Fas ligand expression and phagocytic activity of lpr macrophages were promoted through increased NF-κB activation. Controlling Fas expression on macrophages plays an essential role in maintaining T cell homeostasis in the peripheral immune system. Our data suggest a critical implication to the therapeutic strategies such as transplantation and immunotherapy for immune disorder or autoimmunity related to abnormal Fas expression.
Volume 190(2)
Pages 578-85
Published 2013-1-15
DOI 10.4049/jimmunol.1103794
PII jimmunol.1103794
PMID 23255359
PMC PMC3539689
MeSH Animals Cell Death / immunology Cell Movement / genetics Cell Movement / immunology Fas Ligand Protein / genetics Fas Ligand Protein / immunology Gene Expression Regulation Immunomodulation / genetics Macrophages / immunology* Macrophages / metabolism* Mice Mice, Inbred MRL lpr Mice, Transgenic NF-kappa B / metabolism Phagocytosis / immunology* T-Lymphocytes / immunology* T-Lymphocytes / metabolism* fas Receptor / deficiency*
IF 4.886
Times Cited 5
Mice RBRC00267