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Selected Publication:
Schweintzger, N.
Pathomechanisms of polymorphic light eruption
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] ; 2015. pp.
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- Authors Med Uni Graz:
- Schweintzger Nina
- Advisor:
- Wolf Peter
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- Abstract:
- The exact pathomechanisms of polymorphic light eruption (PLE) are still unknown, but recent evidence suggests a decreased infiltration of neutrophils, macrophages and mast cells upon UV radiation into the skin, which is associated with non-emigration of Langerhans cells (LCs) that are important for the immune response. In contrast, in irradiated skin of healthy individuals LCs migrate to the draining lymph nodes where they might activate regulatory T cells (Treg) which suppress cellular immunity by suppression of auto-reactive T cells. The skin lesions of patients are abating as summer progresses due to a so called “hardening effect” which can also be induced by prophylactic administration of medical photo(chemo) therapy like PUVA, 311nm UVB or UVB. In the present work possible effectors were investigated, that if missing or dysfunctional may render patients with photodermatoses more susceptible to UV radiation. In study part 1 Treg numbers and function were assessed in 30 PLE patients with and without medical phototherapy as well as 19 healthy controls at two time points from March to June of a season from 2012 to 2014. Medical photohardening of 23 PLE patients resulted in a significant increase in the median percentage of circulating Treg (65,6% increase in lymphocyte population (P=0.0049), 32,5% increase in CD4+ T cell population; (P=0.0049)). This was accompanied by an increase in the expression of FoxP3 mRNA (P=0.0083) and relative immunosuppressive function of Treg (P=0.084), comparing the two time points in representative subsets of patients with healthy controls tested. A tendency towards an increase in Treg numbers of PLE patients without medical photohardening was observed, suggesting a natural photohardening by seasonal factors. An increase in Treg levels might counteract the susceptibility to PLE. The latter finding is substantiated by the results of the second part of the thesis where the effects of season on vitamin D levels as well as Treg numbers and function in PLE patients were in-vestigated. A positive correlation of season with vitamin D serum levels (Spearman R = 0,586, Spearman P = 0,0026) was observed. There was no relationship of season or Vitamin D with Treg levels and function, although a seasonal tendency for an increase in relative and absolute Treg numbers was detected. Together this indicates that Treg numbers and Treg suppressive function in PLE patients is independent from 25(OH)D serum levels. By using the mast cell-deficient KitW-Sh/W-Sh mouse model in thesis part 3 a potential mechanistic role of mast cells in reducing the sensitivity to UV radiation through photohardening was determined, identifying a new in vivo model to study photodermatoses. The results from this animal model suggested that mast cells initiated phototolerance through photohardening and provided a recruiting signal to neutrophils and Treg upon UV radiation. While it is well known that mast cell-deficient mice are resistant to UV-induced immune suppression, it was discovered that they are prone to develop photo itch and are more susceptible to UV-induced epidermal hyperplasia as well as skin edema. Together these results indicate that Treg are involved in the pathophysiology of PLE. In addi-tion it is proposed that Treg are affected by UV radiation and/or other potential seasonal fac-tors.