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Protein kinase C transduces the signal for Langerhans' cell migration from the epidermis

G M Halliday1, A D Lucas

  • 1Department of Dermatology, University of Sydney, Royal Prince Alfred Hospital, NSW, Australia.

Immunology
|August 1, 1993
PubMed

Insights

Protein kinase C (PKC) activation triggers Langerhans

Area of Science:

  • Immunology
  • Dermatology
  • Cell Biology

Background:

  • Langerhans' cells (LC) are crucial for initiating skin immune responses by migrating from the epidermis to lymph nodes.
  • The intracellular mechanisms governing LC migration from the epidermis remain largely unelucidated.

Purpose of the Study:

  • To investigate the role of protein kinase C (PKC) in mediating epidermal Langerhans' cell migration.
  • To identify the intracellular signaling pathways involved in LC migration from the skin.

Main Methods:

  • Topical application of a diacylglycerol (DAG) analogue, L-alpha-dioctanoyl glycerol (oDAG), to mouse skin.
  • Assessment of epidermal LC density using Ia+ and J11d+ markers.
  • Tracking of fluorescein isothiocyanate (FITC)-labeled LC migration to local lymph nodes.
  • Inhibition of PKC using palmitoyl-DL-carnitine chloride (PCC) or D-Sphingosine (Sph) to assess its effect on LC migration.

Main Results:

  • Topical oDAG significantly reduced epidermal LC density in mice.
  • oDAG treatment increased the number of FITC-positive cells in draining lymph nodes, confirming LC migration.
  • PKC inhibition by PCC or Sph blocked contact sensitizer-induced LC migration from the epidermis.
  • PKC inhibition did not affect the induction of contact sensitivity itself.

Conclusions:

  • Protein kinase C (PKC) activation is a key intracellular signal that induces Langerhans' cell migration from the epidermis.
  • Disruptions in PKC signaling can impair cutaneous immune responses by hindering LC migration to lymph nodes.
  • PKC acts as a critical transducer in the signaling cascade leading to LC epidermal egress.

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