In silico and multi-dimensional functional interrogation of tissue Tregs reveals novel therapeutics for autoimmunity and inflammation

Abstract

Abstract Many inflammatory and autoimmune diseases present with specific organ manifestations. Understanding the immune process at the site of inflammation may offer important insights into novel therapeutic strategies. To this end, we established a biology platform that allows us to develop a deep understanding of human tissue Treg behavior to enable a next generation of therapeutics aimed at activating these regulatory circuits at the location where the disease manifests. We apply single-cell RNA sequencing and computational tools to our proprietary collection of healthy and diseased tissues to generate a high-resolution map of immune-regulatory pathways. Based on these learnings, we established in vitro culturing conditions that induce the expression of these tissue pathways in primary human Treg. Lastly, we have developed a suite of disease relevant phenotypic assays that allows for multi-dimensional functional interrogation of the mapped tissue Treg pathways in our in vitro-conditioned human primary Treg. This combination of complex in silico tools and translational in vitro assays allows us to identify novel regulatory nodes and forms the foundation of our growing pipeline of a new class of tissue Treg-focused therapeutics for immune-mediated diseases.