Abstract
Stra13, a basic helix-loop-helix transcription factor, is up-regulated upon activation of CD4+ T cells. Here we show that Stra13-deficient mice exhibit defects in several phases of CD4+ T cell activation. In vivo, Stra13 deficiency results in ineffective elimination of activated T and B cells, which accumulate progressively, leading to lymphoid organ hyperplasia. Consequently, aging Stra13-/- mice develop autoimmune disease characterized by accumulation of spontaneously activated T and B cells, circulating autoantibodies, infiltration of T and B lymphocytes in several organs and immune complex deposition in glomeruli. Our studies identify Stra13 as a key regulator of lymphocyte activation that is vital for maintenance of self-tolerance and for constraint of autoimmunity.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / immunology
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Animals
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Apoptosis
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Autoantibodies / biosynthesis
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Autoimmune Diseases / complications
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Autoimmune Diseases / genetics
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Autoimmune Diseases / immunology*
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Basic Helix-Loop-Helix Transcription Factors
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CD4-Positive T-Lymphocytes / immunology*
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CD4-Positive T-Lymphocytes / pathology
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Cell Differentiation
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Chimera
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Cytokines / biosynthesis
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Cytokines / genetics
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Fas Ligand Protein
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Female
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Gene Expression Regulation
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Gene Targeting
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Genotype
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Glomerulonephritis / etiology
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Homeodomain Proteins / genetics
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Homeodomain Proteins / physiology*
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Hyperplasia
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Immune Complex Diseases / etiology
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Lymph Nodes / pathology
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Lymphocyte Activation / physiology*
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Lymphoid Tissue / pathology
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Male
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Membrane Glycoproteins / physiology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Spleen / pathology
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fas Receptor / physiology
Substances
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Autoantibodies
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Basic Helix-Loop-Helix Transcription Factors
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Bhlhe40 protein, mouse
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Cytokines
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Fas Ligand Protein
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Fasl protein, mouse
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Homeodomain Proteins
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Membrane Glycoproteins
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fas Receptor