A critical role for Stat3 signaling in immune tolerance

Immunity. 2003 Sep;19(3):425-36. doi: 10.1016/s1074-7613(03)00232-2.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen-Presenting Cells / drug effects
  • Antigen-Presenting Cells / immunology
  • Antigen-Presenting Cells / metabolism
  • CD4-Positive T-Lymphocytes / immunology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Enzyme Inhibitors / pharmacology
  • Immune Tolerance / physiology*
  • Macrophages / drug effects
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • STAT3 Transcription Factor
  • Signal Transduction / physiology*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • Tyrphostins / pharmacology


  • DNA-Binding Proteins
  • Enzyme Inhibitors
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • Trans-Activators
  • Tyrphostins
  • alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide