Abstract
Defensins are small cationic peptides with antimicrobial properties. They constitute a highly conserved innate immune defense mechanism across species. Based on the arrangement of disulfide-bonds, α- and β-defensins are distinguished in humans. Both types of defensin comprise several distinct molecules that are preferentially expressed at epithelial surfaces and in blood cells. In the last decade, multiple immunomodulatory functions of defensins have been recognized, including chemotactic activity, the promotion of antigen presentation, and modulations of proinflammatory cytokine secretion. These findings suggested a role for defensins not only as a first line of defense, but also as connectors of innate and adaptive immune responses. Recently, increasingly accumulating evidence has indicated that defensins may also be involved in the pathogenesis of autoimmune rheumatic disorders such as systemic lupus erythematosus and rheumatoid arthritis. The current review summarizes the data connecting defensins to autoimmunity.
Highlights
Introduction to DefensinsThe generation of peptides with antimicrobial properties is a highly conserved mechanism of innate immune defense [1,2]
While this review focuses on the potential role of defensins in autoimmune rheumatic disorders, excellent previous reviews cover defensin biology, antimicrobial properties and highlight their various impacts on the immune system [1,2,5,8,11]
HNP1-3 levels in the synovial fluid of Rheumatoid Arthritis (RA) patients are clearly superior to their concentration in blood [53], HNP1-3 were identified to be upregulated in peripheral blood mononuclear cells of RA patients by mRNA micro-array analysis when compared to healthy controls [56]
Summary
The generation of peptides with antimicrobial properties is a highly conserved mechanism of innate immune defense [1,2]. All defensins exert antimicrobial effects against a wide range of pathogens including bacteria, fungi, viruses and parasites [3,4]. Their positive charge facilitates association to membranes followed by the generation of pores that disrupt electrolyte homeostasis, thereby leading to cell death [4]. The antimicrobial activity to a certain pathogen varies with each individual defensin [3,4] Their potent antimicrobial functions and their highly conserved structure across species suggest that the role for defensins initially consisted in direct pathogenic activity. While this review focuses on the potential role of defensins in autoimmune rheumatic disorders, excellent previous reviews cover defensin biology, antimicrobial properties and highlight their various impacts on the immune system [1,2,5,8,11]
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