Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

Patra, V.
Insight into the role of skin microbiome in UV-induced immune modulation and its potential link to pathogenesis of polymorphic light eruption.
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2019. pp.


Autor/innen der Med Uni Graz:
Patra Vijaykumar
Gorkiewicz Gregor
Strobl Herbert
Wolf Peter

Human skin apart from functioning as a physical barricade to stop the entry of pathogens, also hosts innumerable commensal organisms, i.e. the skin microbiome. The skin cells and the immune system constantly interact with microbes, to maintain cutaneous homeostasis, despite the challenges offered by various environmental factors. A major environmental factor affecting the skin is ultraviolet radiation (UV-R) from sunlight. By targeting the cells and molecules within skin, UV-R can trigger the production and release of antimicrobial peptides, affect the innate immune system and ultimately suppress the adaptive cellular immune response. However, the role of the skin microbiome in UV-induced immune suppression has been overlooked. This work addressed the question of microbial involvement in UV-induced immune suppression by using the standard model of contact hypersensitivity in the presence or absence of the microbiome (in germ-free [GF] and disinfected mice). The data indicated that the microbiome inhibits UV-induced immune suppression. Furthermore, the transcriptome analysis (with samples taken 24 hours after UV exposure) showed differential regulation of many genes in the presence or absence of the microbiome, including a predominant expression of pro-inflammatory cytokines versus immunosuppressive cytokines. Moreover, 16s rRNA sequencing revealed that UV exposure indeed affected microbial communities living on the skin. In addition, UV-induced isomerization of urocanic acid from its trans- to cis-form (the latter known to be a strong immune suppressor) in the skin was linked to changes in microbial communities. Furthermore, the work confirmed that UV-B exposure caused epidermal barrier dysfunction as measured by trans-epidermal water loss that could potentially allow microbes or microbial antigens to penetrate the skin. These findings are also of potential significance for a better understanding of the pathophysiology of polymorphic light eruption (PLE) whose primary trigger remains to be uncovered. PLE may be initiated by elements resulting from UV-induced damage to microbial communities of the skin, leading to a cascade of events eventually resulting in the skin rash of the disease. UV-induced stress on microbial communities of the skin could exacerbate inflammatory responses by inducing the innate immune system through antimicrobial peptides (AMPs) such as psoriasin, RNase7, HBD-2, HBD-3 and LL-37. These AMPs also actively take part in initiating adaptive immunity. Abnormalities in AMP expression have been linked to pathological skin conditions such as atopic dermatitis (AD) and psoriasis. Antimicrobial peptide profiling was carried out in PLE skin samples compared with that of healthy, atopic, and psoriatic skin. Compared to healthy skin, there was an increased expression of psoriasin and RNAse7 (both mostly in stratum granulosum of the epidermis), HBD-2 (in the cellular infiltrate of the dermis), and LL37 (mostly in and around blood vessels and glands) in PLE lesional skin, a similar expression profile as observed in psoriatic skin and entirely different to that of AD (with little or no expression of psoriasin, RNAse7, HBD-2, and LL37). HBD-3 was downregulated in PLE compared to its high expression in the epidermis of AD and psoriasis. The role of the skin microbiome in UV-induced immune modulation and the unique profile of differentially expressed AMPs in PLE may be crucial in the pathophysiology of the disease.

© Med Uni Graz Impressum