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Mechanisms of Bifunctional Peptide In Vitro Activity in Modulating Immune Response
Villela, Andrea Lucia
Villela, Andrea Lucia
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Abstract
For many years, millions of people around the world have suffered from autoimmune diseases. Autoimmune diseases are caused by our own immune system when it begins to target and attack part of the body due to recognition of self-tissue as a foreign antigen. Current therapeutic regimes utilize immunosuppressive agents to halt immune cells from recognizing and attacking self-tissues. However, lowering systemic immunity can make patients susceptible to opportunistic infection by pathogens. Therefore, further research is needed to find effective treatments that will regulate a specific subpopulation of the immune system that attacks self-tissue in autoimmune diseases. This study was designed to understand the effect of delivering antigen-specific immunomodulatory peptides on immune activation and their cytotoxicity across various cell lines.This study is aimed to evaluate the effects of parent antigenic peptides and bifunctional peptide inhibitors (BPIs) on the innate and adaptive immune system as potential antigen-specific treatments of autoimmune diseases while not creating toxicity to the cells. To do this, we first evaluate the mechanisms of action of peptides such as OVA323-339, OVA257-264, LABL, OVA323-339BPI, and OVA257-264BPI on bone marrow derived dendritic cells (DCs). The results showed that OVA323-339BPI had the highest effect on the DCs throughout the study. When evaluating the effects on immature DCs (iDCs), OVA257-264BPI had a significant increase in upregulation of costimulatory receptor CD40. The iDCs treated with OVA323-339BPI showed a significant increase in anti-inflammatory response by upregulation of cytokine IL-10. Evaluating matured DCs in the presence of OVA323-339BPI, there was a significant increase in costimulatory receptors CD40 and CD86. When treating splenocytes with the BPIs and their parent antigenic peptides, the results showed increase in intracellular staining of cytokine IL-10 in macrophages for OVA323-339, OVA323-339BPI, and OVA257-264BPI peptides. Additionally, an increase in proliferation of regulatory T cells (Treg) was observed upon peptide OVA323-339BPI treatment of splenocytes. The cell viability study showed that the peptides were not toxic with having OVA323-339 peptide be the lowest cell viability at 91.9% at 10 µM. An additional study involving dynamic light scattering (DLS) was conducted to assess any aggregation. The result showed that there was no aggregation of the peptides in cell media; thus, the peptides used have were in a fully function monomer state.In conclusion, this study found novel information for antigen-specific therapeutics. Further investigation is needed to evaluate the effects of BPIs on bone marrow derived DCs in mice pretreated with BPIs. In addition, the effects of BPIs on a mixture of DCs and CD4+T cells from splenocytes will be evaluated in the future. Based on these findings, more developments can be carried out to target a specific autoimmune disease, optimize the cell targeting, and formulate the BPIs for their delivery.
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2024-05-31
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University of Kansas
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1072427_1.pdf
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Keywords
Bioengineering, Pharmacology, Autoimmune Diseases, Cytokine Expression, Flow Cytometry, Immune System, Immunomodulatory Therapies, Peptides