Doctoral defence in life and medical sciences - Hildur Sigurgrímsdóttir-

On Friday, March 14, 2025, Hildur Sigurgrímsdóttir will defend her doctoral dissertation in life and medical sciences at the Faculty of Medicine, University of Iceland.

The dissertation is titled: The immunomodulatory role of LL-37 in the pathogenesis of psoriasis.

The opponents are Dr. Christopher Griffiths, Professor Emeritus at the University of Manchester, and Dr. Silke Appel, Professor at the University of Bergen.

The supervisor was Björn Rúnar Lúðvíksson, Professor, and the advisor was Jóna Freysdóttir, Professor. In addition to them, the doctoral committee included Guðmundur Hrafn Guðmundsson, Professor, Ingibjörg Harðardóttir, Professor, and Una Bjarnadóttir, Biologist.

Sædís Sævarsdóttir, Professor and Vice Dean of the Faculty of Medicine, will preside over the ceremony, which will take place in the University of Iceland’s Ceremonial Hall and begin at 9:00 AM.

Abstract

Psoriasis is an autoimmune disease of the skin, and the most common form, plaque psoriasis, is characterized by raised, well-demarcated, erythematous plaques with adherent silvery scales. The immunopathogenesis has a mixed Th1 and Th17 inflammatory profile, and keratinocytes in the basal layer of the skin hyper proliferate and do not mature properly. LL-37 is an anti-microbial peptide of the innate immune system that has extensive immunomodulatory functions. In this project, we wanted to further define the immunomodulatory effect of LL-37 upon various immune biomarker secretion by keratinocytes and white blood cells. The dissertation is based on three studies: In the first study, the role of T17 cells in the pathogenesis of psoriasis was corroborated, as the percentage of Th17 and Tc17 cells was reduced following phototherapy. Within the skin, the number of T cells reduced with psoriasis treatment, and the intensity of immunofluorescent staining of IL-17 in the dermis correlated to severity of disease. In the second study, further phenotypic analysis of these skin-homing T cells in psoriasis patients was performed by measuring the expression of the chemokine receptors CXCR3, CCR4, and CCR6. Different chemokine receptor expression patterns emerged when T cells were subtyped based on the expression of CLA and CD103. When peripheral blood mononuclear cells (PBMCs) were stimulated in vitro with two distinct stimulations mimicking the Th1 and Th17 microenvironment, various biomarker secretory patterns emerged, particularly in association with the presence of LL-37. In the third study, keratinocytes were cultured in the same immunomodulatory microenvironment, as previously described for the PBMCs, and their secretory profile analysed. The results demonstrate that primary keratinocytes secrete a wide array of immune biomarkers that can be significantly affected by Th1 and Th17-driven stimulation. Furthermore, their immune biomarker fingerprinting was frequently altered in the presence of LL-37.

About the Doctoral Candidate

Hildur Sigurgrímsdóttir was born in 1986 in Selfoss, Iceland. She graduated from the natural sciences track at Fjölbrautaskóli Suðurlands in 2004 and completed an agricultural degree at the Agricultural University of Iceland in 2007. Hildur began studying biomedical sciences in 2008 and earned an M.Sc. degree in 2013. She then commenced her doctoral studies in life and medical sciences at the University of Iceland in 2015.

Her research project has received funding from the Icelandic Research Fund (Rannís) and the Landspítali University Hospital Science Fund. Alongside her doctoral studies, Hildur has worked at the Department of Immunology at Landspítali University Hospital.

Hildur’s parents are Herborg Pálsdóttir and Sigurgrímur Vernharðsson, and her stepfather is Úlfar Guðmundsson. She is engaged to Svanur Halldórsson.