JunB plays a crucial role in development of regulatory T cells by promoting IL-2 signaling

Mucosal Immunol. 2019 Sep;12(5):1104-1117. doi: 10.1038/s41385-019-0182-0. Epub 2019 Jul 8.


The AP-1 transcription factor JunB plays crucial roles in multiple biological processes, including placental formation and bone homeostasis. We recently reported that JunB is essential for development of Th17 cells, and thus Junb-deficient mice are resistant to experimental autoimmune encephalomyelitis. However, the role of JunB in CD4+ T cells under other inflammatory disease conditions is unknown. Here we show that mice lacking JunB in CD4+ T cells (Junbfl/flCd4-Cre mice) were more susceptible to dextran sulfate sodium (DSS)-induced colitis because of impaired development of regulatory T (Treg) cells. Production of interleukin (IL)-2 and expression of CD25, a high affinity IL-2 receptor component, were decreased in Junb-deficient CD4+ T cells in vitro and in vivo. Naive CD4+ T cells from Junbfl/flCd4-Cre mice failed to differentiate into Treg cells in the absence of exogenously added IL-2 in vitro. A mixed bone marrow transfer experiment revealed that defective Treg development of Junb-deficient CD4+ T cells was not rescued by co-transferred wild-type cells, indicating a significance of the cell-intrinsic defect. Injection of IL-2-anti-IL-2 antibody complexes induced expansion of Treg cells and alleviated DSS-induced colitis in Junbfl/flCd4-Cre mice. Thus JunB plays a crucial role in the development of Treg cells by facilitating IL-2 signaling.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Colitis / etiology
  • Colitis / metabolism
  • Colitis / pathology
  • Dextran Sulfate / adverse effects
  • Disease Models, Animal
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Interferon-gamma / metabolism
  • Interleukin-2 / metabolism*
  • Mice
  • Mice, Transgenic
  • Protein Binding
  • Signal Transduction*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism*
  • Transcription Factors / metabolism*


  • Interleukin-2
  • JunB protein, human
  • Transcription Factors
  • Interferon-gamma
  • Dextran Sulfate