title: T cell-intrinsic and -extrinsic contributions of the IFNAR/STAT1-axis to thymocyte survival.
abstract: STAT1 is an essential part of interferon signaling, and STAT1-deficiency results in heightened susceptibility to infections or autoimmunity in both mice and humans. Here we report that mice lacking the IFNα/β-receptor (IFNAR1) or STAT1 display impaired deletion of autoreactive CD4(+)CD8(+)-T-cells. Strikingly, co-existence of WT T cells restored thymic elimination of self-reactive STAT1-deficient CD4(+)CD8(+)-T cells. Analysis of STAT1-deficient thymocytes further revealed reduced Bim expression, which was restored in the presence of WT T cells. These results indicate that type I interferons and STAT1 play an important role in the survival of MHC class I-restricted T cells in a T cell intrinsic and non-cell intrinsic manner that involves regulation of Bim expression through feedback provided by mature STAT1-competent T cells.
authors.affiliation: Division of Biological Sciences and UCSD Cancer Center, University of California San Diego, La Jolla, California, United States of America.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Moro
authors.forename: Dennis C
authors.initials: DC
authors.lastname: Otero
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Michael
authors.initials: M
authors.lastname: David
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D002453:Cell Cycle; D002454:Cell Differentiation; D005434:Flow Cytometry; D008285:Major Histocompatibility Complex; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000502:physiology*; D050794:STAT1 Transcription Factor / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060168:Thymocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C000606776:Bcl2l11 protein, mouse; C508032:Ifnar1 protein, mouse; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D053633:Receptor, Interferon alpha-beta