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Generation of Immature, Mature and Tolerogenic Dendritic Cells with Differing Metabolic Phenotypes
Published on: June 22, 2016
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.
Abstract:
Given the importance of dendritic cells in the immune response, we investigated the effect of corticosteroids (CS) on the integrity, survival, and function of murine Langerhans cells (LC) in comparison with pimecrolimus, a novel anti-inflammatory drug for the topical treatment of atopic dermatitis. BALB/c mice were treated twice on one day with ethanolic solutions of the compounds. At 24-72 h after the last application, we observed fragmented DNA, caspase-3 activity, and an upregulation of CD95 expression in LC from mice treated with CS but not in LC of pimecrolimus- or vehicle-treated animals. CS-epidermal cell (EC) supernatants but not pimecrolimus-EC supernatants contained significantly lower amounts of soluble factors (GM-CSF, TNF-alpha, IL-1alpha) required for LC survival and maturation than EC supernatants from vehicle-treated mice. With regard to LC maturation, CS but not pimecrolimus inhibited the expression of CD25, CD205, and costimulatory molecules. In line with this, LC from pimecrolimus-treated mice were similar to LC from vehicle-treated mice in their capacity to stimulate antigen-presenting function and migration, whereas LC from CS-treated mice were greatly impaired in these abilities. In summary, our data show for the first time that CS but not pimecrolimus induce apoptosis in LC in situ, implying that the prolonged use of CS could have adverse effects on the skin immune system.

