Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL-37, in a psoriasis mimicking microenvironment

Hildur Sigurgrimsdottir*, Eva Osp Bjornsdottir, Jenna Huld Eysteinsdottir, Jon Hjaltalin Olafsson, Bardur Sigurgeirsson, Bjarni A. Agnarsson, Helga Kristin Einarsdottir, Jona Freysdottir, Bjorn Runar Ludviksson

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Psoriasis is an autoimmune disease driven by a Th17 response linked to the antimicrobial peptide (AMP) LL-37 that has been connected to the induction and chronicity of psoriasis. We show that keratinocytes secrete various immune biomarkers with a direct link to psoriasis immunopathogenesis. Under pro-inflammatory microenvironmental conditions, LL-37 was found to regulate keratinocyte secretion of various immune biomarkers (eg C-X-C motif chemokine ligand (CXCL)8 and interleukin (IL)-1β) and alter extracellular signal-regulated kinase (ERK)1/2 signalling. However, during neutral conditions LL-37 induced a different pattern of keratinocyte immune biomarker secretion (eg vascular endothelial growth factor, CXCL8 and IL-6). Thus, an interesting pattern emerged regarding the immunomodulatory effects of LL-37 on keratinocytes; in general, expression of immune biomarkers that were upregulated in a Th1-like microenvironment was downregulated in the presence of LL-37. In contrast, LL-37 reinforced the Th17 response. In active psoriatic skin lesions, LL-37 expression was found to be significantly upregulated, which was also evident from the unique diffuse epidermic expression pattern not found in healthy skin. Finally, successful phototherapy of psoriasis patients converted this LL-37 inflammatory psoriatic skin pattern into a more localized basal layer expression as found in healthy controls. Thus, these findings demonstrate that LL-37 has a significant role in skin immune homeostasis and that its interplay with keratinocytes may have a more direct role in the immunopathogenesis of psoriasis than previously thought.

Original languageEnglish
Article numbere13096
JournalScandinavian Journal of Immunology
Volume94
Issue number6
DOIs
Publication statusPublished - 18 Aug 2021

Bibliographical note

Publisher Copyright:
© 2021 The Scandinavian Foundation for Immunology.

Other keywords

  • keratinocytes
  • psoriasis and antimicrobial peptides
  • Immunology
  • Sóríasis
  • Ónæmisfræði
  • Psoriasis

Fingerprint

Dive into the research topics of 'Keratinocytes secrete multiple inflammatory and immune biomarkers, which are regulated by LL-37, in a psoriasis mimicking microenvironment'. Together they form a unique fingerprint.

Cite this