Increased dermal expression of chromatin-associated protein HMGB1 and concomitant T-cell expression of the DNA RAGE in patients with psoriasis vulgaris
Received 11 October 2018
Accepted for publication 11 January 2019
Published 12 February 2019 Volume 2019:9 Pages 7—17
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Uwe Wollina
Lisa Strohbuecker,1 Hans Koenen,2 Esther van Rijssen,2 Bram van Cranenbroek,2 Esther Fasse,2 Irma Joosten,2 Andreas Körber,1 Christoph Bergmann3
1Department of Dermatology, University Hospital Essen, 45147 Essen, Germany; 2Department of Laboratory Medicine, Laboratory of Medical Immunology, Radboud University Medical Center, Nijmegen, the Netherlands; 3Department of Otorhinolaryngology, University Hospital Essen, 45147 Essen, Germany
Purpose: Psoriasis vulgaris (PV) is an autoimmune-related chronic inflammatory disease of the skin, with both vascular and metabolic effects. Aggravating factors have been identified that initiate and maintain inflammation, including expression of Th1-, Th17-, and Th22-cell derived cytokines. Recently, we showed that the evolutionarily ancient and highly conserved damage-associated molecular pattern molecule “high mobility group box 1 (HMGB1)” is significantly increased in the serum of PV patients with disease progression and is decreased under standard therapies.
Materials and methods: To better understand the role of HMGB1 in the pathogenesis of PV, we recruited 22 untreated psoriatic patients with either mild or severe disease, defined by the Psoriasis Area Severity Index. We assessed HMGB1 and receptor for advanced glycation end products (RAGE) expression in the skin by immunohistochemistry and analyzed the immune-phenotype of Treg and Th17 cells by flow cytometry.
Results: We found increased staining for HMGB1 in the dermis of psoriatic plaques in comparison to uninvolved skin of patients with PV. In addition, the major histocompatibility complex class III-encoded DNA and HMGB1 RAGE, induced by HMGB1, were highly expressed on psoriatic CD8+ T cells and CD4+ Treg. High expression of HMGB1 in the lesional skin was associated with even higher expression of its receptor, RAGE, on the cell surface of keratinocytes in patients with severe PV.
Conclusion: The presence of HMGB1 and RAGE signaling may impact orchestration of chronic inflammation in PV which might have implications for Treg and Th17 cells.
Keywords: HMGB1, RAGE, psoriasis vulgaris, Th17
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