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TGFbeta inhibits CD1d expression on dendritic cells.

S Ronger-Savle1, J Valladeau, A Claudy

  • 1Inserm U346, Edouard Herriot Hospital, Lyon, France. sandra.ronger-savle@chu-lyon.fr

The Journal of Investigative Dermatology
|January 19, 2005
PubMed
Summary
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Transforming growth factor beta (TGFbeta) inhibits CD1d expression on dendritic cells (DCs). This suggests TGFbeta produced by keratinocytes downregulates CD1d on intraepidermal Langerhans cells, impacting T cell responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Dermatology

Background:

  • The CD1 family of glycoproteins functions as antigen-presenting molecules for T cell responses, particularly presenting lipid and hydrophobic peptide antigens.
  • CD1d-restricted T cells are implicated in autoimmune diseases and tumor immunity.
  • Transforming growth factor beta (TGFbeta) is a polypeptide growth factor with known inhibitory effects on immune cell proliferation and differentiation, including CD1d-restricted natural killer T cells.

Purpose of the Study:

  • To investigate the role of TGFbeta in regulating CD1d expression on dendritic cells (DCs).
  • To determine if TGFbeta influences CD1d transcription and cell surface expression during DC differentiation.

Main Methods:

  • Dendritic cells (DCs) were developed in vitro from peripheral blood mononuclear cells (PBMC) using granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL4), with and without TGFbeta.

Related Experiment Videos

  • Reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry (FACS) analysis using mAb 42.1 were performed on differentiating CD34+ hematopoietic progenitor cells (HPCs).
  • CD1d expression was evaluated on freshly isolated Langerhans cells (LCs) from epidermal sheets.

    • Main Results:

    • DCs cultured with GM-CSF and IL4 expressed CD1d molecules, whereas those cultured with the addition of TGFbeta did not.
    • Both CD1d mRNA levels and cell surface CD1d expression decreased progressively during the differentiation of CD34+ HPCs, a process inhibited by TGFbeta.
    • Freshly recovered intraepidermal LCs showed no measurable levels of CD1d molecules at the cell membrane, consistent with in vitro findings.

    Conclusions:

    • TGFbeta likely inhibits CD1d transcription during the differentiation of DC precursors towards the Langerhans cell (LC) pathway.
    • TGFbeta produced by keratinocytes contributes to the selective downregulation of CD1d expression on intraepidermal-resident LCs.
    • This downregulation of CD1d by TGFbeta may modulate T cell responses within the epidermis.