title: The nuclear receptor nr4a1 controls CD8 T cell development through transcriptional suppression of runx3.
abstract: The NR4A nuclear receptor family member Nr4a1 is strongly induced in thymocytes undergoing selection, and has been shown to control the development of Treg cells; however the role of Nr4a1 in CD8(+) T cells remains undefined. Here we report a novel role for Nr4a1 in regulating the development and frequency of CD8(+) T cells through direct transcriptional control of Runx3. We discovered that Nr4a1 recruits the corepressor, CoREST to suppress Runx3 expression in CD8(+) T cells. Loss of Nr4a1 results in increased Runx3 expression in thymocytes which consequently causes a 2-fold increase in the frequency and total number of intrathymic and peripheral CD8(+) T cells. Our findings establish Nr4a1 as a novel and critical player in the regulation of CD8 T cell development through the direct suppression of Runx3.
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA.
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.
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.
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.
authors.forename: Runpei
authors.initials: R
authors.lastname: Wu
authors.affiliation: Division of Inflammation Biology, La Jolla Institute for Allergy and Immunology, La Jolla, CA.
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.
authors.forename: Catherine C
authors.initials: CC
authors.lastname: Hedrick
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D002454:Cell Differentiation; D056970:Co-Repressor Proteins; D050677:Core Binding Factor Alpha 3 Subunit / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D018655:Lymphocyte Count; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000378:metabolism; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1 / Q000235:genetics* / Q000378:metabolism*; D011485:Protein Binding; D012097:Repressor Proteins / Q000378:metabolism; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D014158:Transcription, Genetic; D018183:Transplantation Chimera
chemical_list: D056970:Co-Repressor Proteins; D050677:Core Binding Factor Alpha 3 Subunit; D009419:Nerve Tissue Proteins; C539818:Nr4a1 protein, mouse; D057105:Nuclear Receptor Subfamily 4, Group A, Member 1; C485650:Rcor2 protein, mouse; D012097:Repressor Proteins