Presenting Author: Hannah Riley Knight
, Graduate Student at Univ. of Chicago Pritzker Sch. of Molecular Engr.
Abstract:
Trained immunity is a form of innate immune memory characterized by epigenetic and metabolic reprogramming in response to specific stimuli. This rewiring can increase cytokine secretion and other effector responses to pathogens, making it desirable for non-specific protection against diseases. Despite the promise of training for next-generation therapeutic design, most of our current understanding is limited to complex and heterogeneous biologically derived molecules, such as β-glucan or the BCG vaccine. Small molecules with tunable pharmacokinetics and delivery modalities may be better suited for inducing trained immunity in therapeutic settings. We screened a library of 2000 compounds to identify alternative small molecule inducers of trained immunity. Identification of such compounds can improve our understanding of innate immune memory and broaden the scope of its clinical applications. We identified over 2 dozen small molecules in several chemical classes that induce a training phenotype in the absence of initial immune activation, which is a clinical limitation of traditional inducers of training. We chose 7 of these top candidates to characterize via ATAC-sequencing and establish training activity in vivo. Through this work, we have more than doubled the number of compounds known to induce trained immunity, creating new avenues for the therapeutic applications of innate immune training.
High-throughput screen identifies non-inflammatory small molecule inducers of trained immunity
Category
Poster and Podium (Block Symposium)
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Date: May 5 Presentation Time: 03:15 PM to 04:30 PM Room: Exhibit Hall F1