title: Autoregulation of Th1-mediated inflammation by twist1.
abstract: The basic helix-loop-helix transcriptional repressor twist1, as an antagonist of nuclear factor kappaB (NF-kappaB)-dependent cytokine expression, is involved in the regulation of inflammation-induced immunopathology. We show that twist1 is expressed by activated T helper (Th) 1 effector memory (EM) cells. Induction of twist1 in Th cells depended on NF-kappaB, nuclear factor of activated T cells (NFAT), and interleukin (IL)-12 signaling via signal transducer and activator of transcription (STAT) 4. Expression of twist1 was transient after T cell receptor engagement, and increased upon repeated stimulation of Th1 cells. Imprinting for enhanced twist1 expression was characteristic of repeatedly restimulated EM Th cells, and thus of the pathogenic memory Th cells characteristic of chronic inflammation. Th lymphocytes from the inflamed joint or gut tissue of patients with rheumatic diseases, Crohn's disease or ulcerative colitis expressed high levels of twist1. Expression of twist1 in Th1 lymphocytes limited the expression of the cytokines interferon-gamma, IL-2, and tumor necrosis factor-alpha, and ameliorated Th1-mediated immunopathology in delayed-type hypersensitivity and antigen-induced arthritis.
authors.affiliation: German Rheumatism Research Center Berlin, 10117 Berlin, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Niesner
authors.forename: Inka
authors.initials: I
authors.lastname: Albrecht
authors.forename: Marko
authors.initials: M
authors.lastname: Janke
authors.forename: Cornelia
authors.initials: C
authors.lastname: Doebis
authors.forename: Christoph
authors.initials: C
authors.lastname: Loddenkemper
authors.forename: Maria H
authors.initials: MH
authors.lastname: Lexberg
authors.forename: Katharina
authors.initials: K
authors.lastname: Eulenburg
authors.forename: Stephan
authors.initials: S
authors.lastname: Kreher
authors.forename: Juliana
authors.initials: J
authors.lastname: Koeck
authors.forename: Ria
authors.initials: R
authors.lastname: Baumgrass
authors.forename: Kerstin
authors.initials: K
authors.lastname: Bonhagen
authors.forename: Thomas
authors.initials: T
authors.lastname: Kamradt
authors.forename: Philipp
authors.initials: P
authors.lastname: Enghard
authors.forename: Jens Y
authors.initials: JY
authors.lastname: Humrich
authors.forename: Sascha
authors.initials: S
authors.lastname: Rutz
authors.forename: Ulf
authors.initials: U
authors.lastname: Schulze-Topphoff
authors.forename: Orhan
authors.initials: O
authors.lastname: Aktas
authors.forename: Sina
authors.initials: S
authors.lastname: Bartfeld
authors.forename: Helena
authors.initials: H
authors.lastname: Radbruch
authors.forename: Ahmed N
authors.initials: AN
authors.lastname: Hegazy
authors.forename: Max
authors.initials: M
authors.lastname: Löhning
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Baumgart
authors.forename: Rainer
authors.initials: R
authors.lastname: Duchmann
authors.forename: Martin
authors.initials: M
authors.lastname: Rudwaleit
authors.forename: Thomas
authors.initials: T
authors.lastname: Häupl
authors.forename: Inna
authors.initials: I
authors.lastname: Gitelman
authors.forename: Veit
authors.initials: V
authors.lastname: Krenn
authors.forename: Joachim
authors.initials: J
authors.lastname: Gruen
authors.forename: Jochen
authors.initials: J
authors.lastname: Sieper
authors.forename: Martin
authors.initials: M
authors.lastname: Zeitz
authors.forename: Bertram
authors.initials: B
authors.lastname: Wiedenmann
authors.forename: Frauke
authors.initials: F
authors.lastname: Zipp
authors.forename: Alf
authors.initials: A
authors.lastname: Hamann
authors.forename: Michal
authors.initials: M
authors.lastname: Janitz
authors.forename: Alexander
authors.initials: A
authors.lastname: Scheffold
authors.forename: Gerd R
authors.initials: GR
authors.lastname: Burmester
authors.forename: Hyun D
authors.initials: HD
authors.lastname: Chang
authors.forename: Andreas
authors.initials: A
authors.lastname: Radbruch
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D001483:Base Sequence; D003093:Colitis, Ulcerative / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003424:Crohn Disease / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D007249:Inflammation / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018664:Interleukin-12 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D009687:Nuclear Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D009687:Nuclear Proteins; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; C067250:Twist1 protein, mouse; D018664:Interleukin-12