Toll like Receptor 2 engagement on CD4+ T cells promotes TH9 differentiation and function

Eur J Immunol. 2017 Sep;47(9):1513-1524. doi: 10.1002/eji.201646846. Epub 2017 Jul 18.

Abstract

We have recently demonstrated that mycobacterial ligands engage Toll like receptor 2 (TLR2) on CD4+ T cells and up-regulate T-cell receptor (TCR) triggered Th1 responses in vitro and in vivo. To better understand the role of T-cell expressed TLR2 on CD4+ T-cell differentiation and function, we conducted a gene expression analysis of murine naïve CD4+ T-cells stimulated in the presence or absence of TLR2 co-stimulation. Unexpectedly, naïve CD4+ T-cells co-stimulated via TLR2 showed a significant up-regulation of Il9 mRNA compared to cells co-stimulated via CD28. Under TH9 differentiation, we observed up-regulation of TH9 differentiation, evidenced by increases in both percent of IL-9 secreting cells and IL-9 in culture supernatants in the presence of TLR2 agonist both in polyclonal and Ag85B cognate peptide specific stimulations. Under non-polarizing conditions, TLR2 engagement on CD4+ T-cells had minimal effect on IL-9 secretion and TH9 differentiation, likely due to a prominent effect of TLR2 signaling on IFN-γ secretion and TH1 differentiation. We also report that, TLR2 signaling in CD4+ T cells increased expression of transcription factors BATF and PU.1, known to positively regulate TH9 differentiation. These results reveal a novel role of T-cell expressed TLR2 in enhancing the differentiation and function of TH9 T cells.

Keywords: BATF; CD4+; IL9; PU.1; T cells; TH9 T cells; Toll like receptor 2.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acyltransferases / immunology
  • Animals
  • Antigens, Bacterial / immunology
  • Bacterial Proteins / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • Cell Differentiation
  • Cells, Cultured
  • Cytokines / metabolism
  • Humans
  • Interferon-gamma / metabolism
  • Interleukin-9 / genetics
  • Interleukin-9 / metabolism*
  • Lymphocyte Activation
  • Mice
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins / metabolism
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology*
  • Toll-Like Receptor 2 / immunology
  • Toll-Like Receptor 2 / metabolism*
  • Trans-Activators / metabolism
  • Transcriptome

Substances

  • Antigens, Bacterial
  • Bacterial Proteins
  • Cytokines
  • Interleukin-9
  • Proto-Oncogene Proteins
  • Receptors, Antigen, T-Cell
  • Toll-Like Receptor 2
  • Trans-Activators
  • proto-oncogene protein Spi-1
  • Interferon-gamma
  • Acyltransferases
  • antigen 85B, Mycobacterium tuberculosis