title: IL-23 promotes TCR-mediated negative selection of thymocytes through the upregulation of IL-23 receptor and RORγt.
abstract: Transient thymic involution is frequently found during inflammation, yet the mode of action of inflammatory cytokines is not well defined. Here we report that interleukin-23 (IL-23) production by the thymic dendritic cells (DCs) promotes apoptosis of the CD4(hi)CD8(hi) double-positive (DP) thymocytes. A deficiency in IL-23 signalling interferes with negative selection in the male D(b)/H-Y T-cell receptor (TCR) transgenic mice. IL-23 plus TCR signalling results in significant upregulation of IL-23 receptor (IL-23R) expressed predominantly on CD4(hi)CD8(hi)CD3(+)αβTCR(+) DP thymocytes, and leads to RORγt-dependent apoptosis. These results extend the action of IL-23 beyond its peripheral effects to a unique role in TCR-mediated negative selection including elimination of natural T regulatory cells in the thymus.
authors.affiliation: 1] Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA [2] Department Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.affiliation: Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hsu
authors.affiliation: Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: PingAr
authors.initials: P
authors.lastname: Yang
authors.affiliation: Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Bao
authors.initials: B
authors.lastname: Luo
authors.affiliation: Department of Pediatrics, University of Washington, Seattle, Washington 98195, USA.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Oukka
authors.affiliation: Division of Pulmonary, Allergy & Critical Care, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Claude H
authors.initials: CH
authors.lastname: Steele
authors.affiliation: Merck Research Laboratories, Palo Alto, California 94304, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Cua
authors.affiliation: Clinical Pathology & Anatomic Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: William E
authors.initials: WE
authors.lastname: Grizzle
authors.affiliation: 1] Division of Clinical Immunology & Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA [2] Birmingham VA Medical Center, Birmingham, Alabama 35233, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: D000818:Animals; D017209:Apoptosis; D053759:Interleukin-23 / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000378:metabolism*; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D018123:Receptors, Interleukin / Q000378:metabolism*; D060168:Thymocytes / Q000502:physiology*
chemical_list: D053759:Interleukin-23; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D011948:Receptors, Antigen, T-Cell; D018123:Receptors, Interleukin; C528688:interleukin-23 receptor, mouse