2 research outputs found
Assessing B Cell Differentiation Following Asbestos Fiber Exposure
B cells are the main pathogenesis drivers in autoimmune diseases. Subtypes of B cells, known as B regulatory (Breg) or B10 cells contain a suppressive function, which down regulates the immune response. This is primarily conducted by IL-10, which is an inhibitory cytokine that is produced by the B10 subset. Recent evidence indicates that exposure to different asbestos fiber cause the activation of the immune system, however there is a difference in the response created by each fiber type. The Libby amphibole (LA) fiber leads to autoimmune response, whereas Chrysotile (Chry) fiber exposure does not. We hypothesize that this difference occurs because Chry exposure increases the production of B10 cell to keep the immune system suppressed. To test this, we will collect mouse splenocytes and expose the cells to the different asbestos fibers for 48 or 96 hours. As a control, the splenocytes will be exposed to the proteins, BAFF or IL-21. These proteins have been shown to stimulate proliferation of B10 cells. Next, we will use antibodies against cell surface markers and flow cytometry in order to identify B cell subtypes. Thus, we can investigate B cell differentiation, with the hypothesis that LA will decrease Breg differentiation, whereas Chry will increase Breg differentiation. This investigation will increase our understanding of how different asbestos fibers induce Breg production
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A Drug Repurposing Approach Reveals Targetable Epigenetic Pathways in Plasmodium vivax Hypnozoites.
Radical cure of Plasmodium vivax malaria must include elimination of quiescent "hypnozoite" forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets, we screened the Repurposing, Focused Rescue, and Accelerated Medchem library against P. vivax liver stages and identified the DNA methyltransferase inhibitors hydralazine and cadralazine as active against hypnozoites. We then used bisulfite sequencing and immunostaining to identify cytosine modifications in the infectious stage (sporozoites) and liver stages, respectively. A subsequent screen of epigenetic inhibitors revealed hypnozoites are broadly sensitive to histone acetyltransferase and methyltransferase inhibitors, indicating that several epigenetic mechanisms are likely modulating hypnozoite persistence. Our data present an avenue for the discovery and development of improved radical cure antimalarials