Defensins: Potential Effectors in Autoimmune Rheumatic Disorders

Abstract

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.

Gene Expression Deconvolution for Uncovering Molecular Signatures in Response to Therapy in Juvenile Idiopathic Arthritis

“…α-defensins are homologous peptides expressed by cells participating in the innate immune response including neutrophils, macrophages and intestinal Paneth cells [ 29 ]. In addition to their role in innate immunity, recent studies showed that α-defensins may also play a role in the pathogenesis of autoimmune diseases [ 30 ]. DEFA1-3 (α-defensins 1–3) increase secretion of pro-inflammatory molecules and enhance the presentation of costimulatory molecules on T-cells [ 31 , 32 ].…”

<p>A Synthetic Peptide 2Abz²³S²⁹ Reduces Bacterial Titer and Induces Pro-Inflammatory Cytokines in a Murine Model of Urinary Tract Infection</p>

“…37 Finally, it should be mentioned that HNP-1 as an immunostimulatory molecule is chemotactic for naive CD45RA/CD4 T cells, CD8 T cells, immature dendritic cells, and monocytes. 38 So the capacity for 2Abz 23 S 29 to increase one cytokine and decrease another cytokine might depend on the accumulation of immune populations and their activity within the bladder during UTI infection. In the future, the antimicrobial and immune-modulatory effect of the test peptide can be strengthened by the addition of some type of comparison of the inflammatory cell population in the urine and bladder.…”

RP-HPLC-ESI-IT Mass Spectrometry Reveals Significant Variations of the Human Salivary Protein Profile Associated with Predominantly Antibody Deficiencies

“…Since previous studies reported defective functions and abnormality in the maturation of neutrophils [12] and NK cells [13] in CVID patients, it would be interesting to evaluate if the low levels and frequencies of salivary α-defensins 1-4 we observed mainly in the CVID subgroup may be associated with the status of recurrent infections typically observed in these patients. It appears interesting to underline that immunomodulatory functions were suggested for the α-defensins, as well as their involvement in the communication between the innate and adaptive immune systems [49]. Indeed, it was demonstrated that α-defensins can transfer from neutrophils to memory B cells to exert their bactericidal activity against Streptococcus pneumoniae [50].…”