A critical role for Stat3 signaling in immune tolerance.
Antigen-presenting cells (APCs) can induce T cell activation as well as T cell tolerance. The molecular mechanisms by which APCs regulate this critical decision of the immune system are not well understood. Here we show that Stat3 signaling plays a critical role in the induction of antigen-specific T cell tolerance. Targeted disruption of Stat3 signaling in APCs resulted in priming of antigen-specific CD4(+) T cells in response to an otherwise tolerogenic stimulus in vivo. Furthermore, APCs devoid of Stat3 effectively break antigen-specific T cell anergy in vitro. Conversely, increased Stat3 activity in APCs led to impaired antigen-specific T cell responses. Stat3 signaling provides, therefore, a novel molecular target for manipulation of immune activation/tolerance, a central decision with profound implications in autoimmunity, transplantation, and cancer immunotherapy.
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007108:Immune Tolerance / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D051379:Mice; D050796:STAT3 Transcription Factor; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D020032:Tyrphostins / Q000494:pharmacology
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; D015534:Trans-Activators; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide