Corticosteroids but not pimecrolimus affect viability, maturation and immune function of murine epidermal Langerhans

Wolfram Hoetzenecker1, Josef G Meingassner, Rupert Ecker

  • 1DIAID, Department of Dermatology, Medical University of Vienna, Austria.

Insights

Corticosteroids (CS) induce apoptosis in mouse Langerhans cells (LC), impairing skin immunity. Pimecrolimus did not cause these adverse effects, suggesting safer topical use for skin conditions.

Area of Science:

  • Immunology
  • Dermatology

Background:

  • Dendritic cells, particularly Langerhans cells (LC), are crucial for skin immune responses.
  • Corticosteroids (CS) are widely used anti-inflammatory drugs, but their effects on LC are not fully understood.
  • Pimecrolimus is a novel topical anti-inflammatory agent for atopic dermatitis.

Purpose of the Study:

  • To investigate the impact of corticosteroids (CS) on the integrity, survival, and function of murine Langerhans cells (LC).
  • To compare the effects of CS with pimecrolimus on LC in situ.
  • To assess the potential adverse effects of prolonged CS use on the skin immune system.

Main Methods:

  • BALB/c mice were topically treated with CS, pimecrolimus, or vehicle.
  • LC apoptosis was assessed via DNA fragmentation, caspase-3 activity, and CD95 expression.
  • Soluble factors (GM-CSF, TNF-alpha, IL-1alpha) in epidermal cell supernatants were quantified.
  • LC maturation markers (CD25, CD205, costimulatory molecules) were analyzed.
  • LC antigen-presenting function and migration capacity were evaluated.

Main Results:

  • CS treatment induced DNA fragmentation, caspase-3 activity, and CD95 upregulation in LC.
  • Pimecrolimus did not induce these markers of apoptosis in LC.
  • CS-treated epidermal cell supernatants had significantly lower levels of LC survival and maturation factors.
  • CS inhibited LC maturation markers and impaired their antigen-presenting function and migration.
  • Pimecrolimus-treated LC function was comparable to controls.

Conclusions:

  • Corticosteroids induce apoptosis in Langerhans cells in situ.
  • Pimecrolimus does not induce LC apoptosis and preserves their function.
  • Prolonged corticosteroid use may adversely affect the skin's immune system, highlighting potential risks compared to pimecrolimus.