title: Transcriptional regulator Id2 is required for the CD4 T cell immune response in the development of experimental autoimmune encephalomyelitis.
abstract: An effective immune response to Ag challenge is critically dependent on the size of the effector cell population generated from clonal activation of Ag-specific T cells. The transcription network involved in regulating the size of the effector population, particularly for CD4 Th cells, is poorly understood. In this study, we investigate the role of Id2, an inhibitor of E protein transcription factors, in the generation of CD4 effectors. Using a T cell-specific conditional Id2 knockout mouse model, we show that inhibitor of DNA binding (Id)2 is essential for the development of experimental autoimmune encephalomyelitis. Although Ag-specific and IL-17-producing CD4 T cells are produced in these mice, the activated CD4 T cells form a smaller pool of effector cells in the peripheral lymphoid organs, exhibit reduced proliferation and increased cell death, and are largely absent in the CNS. In the absence of Id2, E protein targets, including the proapoptotic protein Bim and SOCS3, are expressed at higher levels among activated CD4 T cells. This study reveals a critical role of Id2 in the control of effector CD4 T cell population size and the development of a Th17-mediated autoimmune disease.
authors: Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Yen-Yu
authors: YY
authors: Lin
authors: Mary E
authors: ME
authors: Jones-Mason
authors: Makoto
authors: M
authors: Inoue
authors: Anna
authors: A
authors: Lasorella
authors: Antonio
authors: A
authors: Iavarone
authors: Qi-Jing
authors: QJ
authors: Li
authors: Mari L
authors: ML
authors: Shinohara
authors: Yuan
authors: Y
authors: Zhuang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D055879:Gene Knock-In Techniques; D006801:Humans; D051797:Inhibitor of Differentiation Protein 2 / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology*; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D016192:Resting Phase, Cell Cycle / Q000235:genetics / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D014158:Transcription, Genetic / Q000276:immunology*
chemical_list: C497452:Idb2 protein, mouse; D051797:Inhibitor of Differentiation Protein 2