title: Cutting Edge: The Orphan Nuclear Receptor Nr4a1 Regulates CD8+ T Cell Expansion and Effector Function through Direct Repression of Irf4.
abstract: The transcription factor IFN regulatory factor (IRF)4 was shown to play a crucial role in the protective CD8(+) T cell response; however, regulation of IRF4 expression in CD8(+) T cells remains unclear. In this article, we report a critical role for Nr4a1 in regulating the expansion, differentiation, and function of CD8(+) T cells through direct transcriptional repression of Irf4. Without Nr4a1, the regulation of IRF4 is lost, driving an increase in Irf4 expression and, in turn, resulting in a faster rate of CD8 T cell proliferation and expansion. Nr4a1-deficient mice show increases in CD8 T cell effector responses with improved clearance of Listeria monocytogenes. Our data support a novel and critical role for Nr4a1 in the regulation of CD8(+) T cell expansion and effector function through transcriptional repression of Irf4.
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Heba N
authors.initials: HN
authors.lastname: Nowyhed
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Tridu R
authors.initials: TR
authors.lastname: Huynh
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Graham D
authors.initials: GD
authors.lastname: Thomas
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037.
authors.forename: Amy
authors.initials: A
authors.lastname: Blatchley
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037 hedrick@lji.org.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Hedrick
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D050835:Interferon Regulatory Factors / Q000235:genetics / Q000276:immunology*; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics / Q000276:immunology*; D000099218:Interferon Regulatory Factor-4
chemical_list: D050835:Interferon Regulatory Factors; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; D000099218:Interferon Regulatory Factor-4; C539818:Nr4a1 protein, mouse