There is a growing incidence worldwide of conditions necessitating lifelong immunomodulatory therapy. Inflammatory skin diseases such as psoriasis, which affects up to 4% of the Western population, can be highly debilitating. Current therapies are not consistently efficacious for all patients and carry a risk of substantial adverse effects. New therapies that provide targeted suppression of inappropriate inflammation are needed. Immunomodulatory peptides offer potential for targeting specific immune pathways and have previously been identified from several natural sources. We have uncovered a novel role for a human peptide (RP23) in modulating and suppressing inflammation. RP23 was produced by chemical synthesis with modifications to enhance solubility and ease of production. Culture of primary human or murine macrophages with RP23 led to reduced IL-12(p40), IL-6 and MCP-1 release after TLR-stimulation. In a mouse model of contact dermatitis, a single injection of RP23 prior to sensitisation significantly suppressed elicitation of inflammation, as measured by a reduction in ear thickness and inflammatory infiltrate. Further, in a murine model of imiquimod-induced psoriasis, RP23 reduced erythema, skin thickness and scaling. This immunomodulatory effect was isolated to the area in which RP23 was delivered, unlike topical application of a glucocorticoid which caused systemic immune suppression. When RP23 was injected intra-dermally into human skin explants it reduced spontaneous activation of dermal dendritic cells. Importantly, there was no cytotoxicity detected in vivo or when tested across multiple cell lines. RP23 therefore offers potential as a novel, locally acting peptide-based therapy for patients seeking improved management of inflammatory skin diseases.
About the Speaker
Scott Byrne is an Associate Professor based at The Westmead Institute for Medical Research. As an immunologist who specialises in photomedicine, Scott is internationally known for his discoveries on how exposure of the skin to solar ultraviolet (UV) radiation can cause skin cancer but is also critical to protect us from autoimmune diseases. A focus of Scotts work has been to identify immune cells and molecules that can be targeted therapeutically by novel immune modulators.
Scott was awarded his PhD in 2002 during which time he discovered that both UVB and UVA suppress cell-mediated immunity. He also discovered that a major mechanism by which UV suppresses immunity is via the activation of a unique subset of regulatory B cells. While training as a postdoc at the MD Anderson Cancer Center, Scott discovered that UV activates the CXCL12 chemokine pathway and that this drives mast cells to migrate from the skin to draining lymph nodes where they mediate UV-immunosuppression. He also discovered that platelet activating factor (PAF) and serotonin receptor signalling is required for UV-activation of regulatory B cells.
Upon his return to Australia, Scott was awarded a Cancer Institute NSW fellowship which enabled him set up the Cellular Photoimmunology Group and design an innovative method of delivering the CXCR4 antagonist AMD3100 to block UV-immunosuppression and carcinogenesis. Other contributions to immunology include his discovery that activation of the alternative complement pathway and upregulation of IL-33 in the skin are key mechanisms driving UV-immunosuppression. More recently, Scott and his team have revealed that UV-activation of regulatory B cells not only drives skin carcinogenesis, but is responsible for UV protection from autoimmune diseases that target the central nervous system.
In recognition of his contributions, Scott has been the recipient of a number of prestigious research awards including a NSW Young Tall Poppy Science award (2009), The European Society for Photobiology Young Investigator Award (2011), The Asia & Oceania Society for Photobiology Award for Young Scientists (2015), and The University of Sydney Vice-Chancellor’s Award for Outstanding Research & Teaching (2016). This year he was awarded the prestigious Finsen Lecturer award by the International Union of Photobiology (2019).