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Human Keratinocytes Inhibit CD4+ T-Cell Proliferation through TGFB1 Secretion and Surface Expression of HLA-G1 and

Guillaume Mestrallet1,2, Frédéric Auvré1,2, Chantal Schenowitz3,4

  • 1CEA, Laboratory of Genomics and Radiobiology of Keratinopoiesis, Institute of Cellular and Molecular Radiobiology, Francois Jacob Institute of Biology, DRF, 91000 Evry, France.

Cells
|July 2, 2021
PubMed

Insights

Human skin cells (keratinocytes) suppress immune T-cell activity by releasing factors and expressing immune checkpoints like HLA-G1. This finding highlights keratinocytes

Area of Science:

  • Immunology
  • Dermatology
  • Cell Biology

Background:

  • Human skin's protective functions involve complex interactions between immune and epithelial cells.
  • The precise mechanisms of keratinocyte-immune cell communication are not fully understood.
  • Understanding these interactions is crucial for tissue immunity and therapeutic applications.

Purpose of the Study:

  • To investigate the immunomodulatory role of human epidermal keratinocytes on T-cell proliferation.
  • To identify the specific factors and molecules involved in keratinocyte-mediated immune suppression.
  • To explore the potential of keratinocytes in allogeneic cell therapy.

Main Methods:

  • Cultured human epidermal keratinocytes were co-cultured with allogenic CD4+ T-cells.
  • Analysis of soluble factors secreted by keratinocytes.
  • Assessment of cell-surface immune checkpoint expression (HLA-G1, PD-L1).
  • Overexpression of HLA-G1 using an inducible vector.

Main Results:

  • Keratinocytes significantly inhibited CD4+ T-cell proliferation under normal and inflammatory conditions.
  • Inhibitory effects were mediated by secreted factors, including TGF-β1.
  • Cell-surface expression of immune checkpoints HLA-G1 and PD-L1 was observed.
  • First-time description of HLA-G1 protein expression in healthy human skin.
  • Overexpression of HLA-G1 enhanced keratinocytes' immunosuppressive properties.

Conclusions:

  • Human epidermal keratinocytes possess potent immunosuppressive capabilities against T-cells.
  • HLA-G1 and PD-L1 are key mediators of keratinocyte-driven immunomodulation in skin.
  • Keratinocytes, particularly with enhanced HLA-G1 expression, show promise for allogeneic cell therapy applications.
Keywords:
HLA-G1PD-L1TGFB1human keratinocytesimmunomodulationskin immunitytolerance

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