Deficiency in T follicular regulatory cells promotes autoimmunity

J Exp Med. 2018 Mar 5;215(3):815-825. doi: 10.1084/jem.20170901. Epub 2018 Jan 29.


T follicular regulatory (Tfr) cells are a new subset of regulatory T (T reg) cells localized in the germinal center to limit the humoral response. Until now, the physiological function of Tfr cells has been largely unknown. In this study, we developed a Bcl6fl/flFoxp3Cre mouse to analyze the function of Tfr cells in immune and autoimmune responses. These mice exhibited enhanced immunity to influenza virus; moreover, Bcl6fl/flFoxp3Cre/Cre mice developed late-onset spontaneous autoimmune diseases, affecting the salivary glands with lymphocyte infiltration and antibody deposition. In a mouse experimental Sjögren's syndrome model, ablation of Bcl6 in T reg cells greatly enhanced disease development. Conversely, Bcl6fl/flCd4Cre mice were protected in the model. Thus, our study indicates that Tfr cells control autoimmune diseases and can be targeted in infectious and autoimmune disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmunity*
  • Female
  • Forkhead Transcription Factors / metabolism
  • Germinal Center / metabolism
  • Immunity, Humoral
  • Integrases / metabolism
  • Mice, Knockout
  • Orthomyxoviridae / physiology
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology
  • Proto-Oncogene Proteins c-bcl-6 / metabolism
  • Sjogren's Syndrome / immunology
  • Sjogren's Syndrome / pathology
  • T-Lymphocytes, Regulatory / immunology*


  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Proto-Oncogene Proteins c-bcl-6
  • Cre recombinase
  • Integrases