title: CD28-inducible transcription factor DEC1 is required for efficient autoreactive CD4+ T cell response.
abstract: During the initial hours after activation, CD4(+) T cells experience profound changes in gene expression. Co-stimulation via the CD28 receptor is required for efficient activation of naive T cells. However, the transcriptional consequences of CD28 co-stimulation are not completely understood. We performed expression microarray analysis to elucidate the effects of CD28 signals on the transcriptome of activated T cells. We show that the transcription factor DEC1 is highly induced in a CD28-dependent manner upon T cell activation, is involved in essential CD4(+) effector T cell functions, and participates in the transcriptional regulation of several T cell activation pathways, including a large group of CD28-regulated genes. Antigen-specific, DEC1-deficient CD4(+) T cells have cell-intrinsic defects in survival and proliferation. Furthermore, we found that DEC1 is required for the development of experimental autoimmune encephalomyelitis because of its critical role in the production of the proinflammatory cytokines GM-CSF, IFN-γ, and IL-2. Thus, we identify DEC1 as a critical transcriptional mediator in the activation of naive CD4(+) T cells that is required for the development of a T cell-mediated autoimmune disease.
authors.affiliation: Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA.
authors.forename: Marc
authors.initials: M
authors.lastname: Martínez-Llordella
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Esensten
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Bailey-Bucktrout
authors.forename: Robert H
authors.initials: RH
authors.lastname: Lipsky
authors.forename: Ann
authors.initials: A
authors.lastname: Marini
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Mohamed
authors.initials: M
authors.lastname: Mughal
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
authors.forename: Dennis D
authors.initials: DD
authors.lastname: Taub
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
mesh_terms: D000818:Animals; D015551:Autoimmunity; D018106:CD28 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation; D016207:Cytokines / Q000096:biosynthesis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007376:Interleukin-2 / Q000378:metabolism; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*
chemical_list: D018106:CD28 Antigens; D016207:Cytokines; C403671:DELEC1 protein, human; D018836:Inflammation Mediators; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D025521:Tumor Suppressor Proteins