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

• Published in: Scandinavian journal of immunology Vol. 94; no. 6; pp. e13096 - n/a
• Main Authors: Sigurgrimsdottir, Hildur, Bjornsdottir, Eva Osp, Eysteinsdottir, Jenna Huld, Olafsson, Jon Hjaltalin, Sigurgeirsson, Bardur, Agnarsson, Bjarni A., Einarsdottir, Helga Kristin, Freysdottir, Jona, Ludviksson, Bjorn Runar
• Format: Journal Article
• Language: English
• Published: Oxford Wiley Subscription Services, Inc 01.12.2021
• Subjects: Antimicrobial agents; Antimicrobial peptides; Autoimmune diseases; Biomarkers; Chemokines; Extracellular signal-regulated kinase; Helper cells; Homeostasis; Immunomodulation; Immunopathogenesis; Inflammation; Keratinocytes; Lymphocytes T; Microenvironments; Mimicry; Phototherapy; Psoriasis; psoriasis and antimicrobial peptides; Skin diseases; Skin lesions; Vascular endothelial growth factor
• ISSN: 0300-9475; 1365-3083
• DOI: 10.1111/sji.13096

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.