Engineered cell sensors for autoimmune monitoring

The National Institute of Allergy and Infectious Diseases awarded the Regents of the University of Michigan $100,228 on October 7, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to engineer cell-based sensors for autoimmune disease detection and monitoring.

The project, titled "Engineered Cell Sensors for Autoimmune Monitoring," develops synthetic cell receptors using Modular Extracellular Sensor Architecture (MESA) to detect interleukin-23 (IL-23), a key driver of autoimmune pathogenesis in diseases such as multiple sclerosis. The work addresses the diagnostic delay in autoimmune disease—currently averaging 4.6 years and 4.8 physicians—by enabling continuous IL-23 monitoring to aid both initial diagnosis and treatment monitoring in patients with suspected or confirmed autoimmune disease. The research plan encompasses three specific aims: incorporating IL-23–specific binders into existing MESA receptors and screening for functional designs; modifying receptor geometry to amplify signal-to-noise ratio; and developing a biomaterial encapsulation platform to validate MESA sensors in vivo. MESA receptors trigger internal cell responses to produce fluorescent reporter protein upon binding a soluble target, with fluorescence output corresponding to biomarker detection above a specified threshold.

Work is performed at the University of Michigan in Ann Arbor, Michigan, with performance ending April 30, 2028. The funding is classified as a Project Grant.

Abstract

The global incidence of autoimmune diseases grows annually. On average, autoimmune diseases require 4.6 years and 4.8 physicians to receive an accurate diagnosis. This is in part due to the multiple strategies needed for diagnosis which extend the timeline to receive treatment. Early detection and treatment of autoimmune diseases prevents the progression of more severe diseases. The cytokine interleukin-23 (IL-23) is a key driver of autoimmune pathogenesis in diseases like multiple sclerosis, and the continuous monitoring of IL-23 in people suspected of having an autoimmune disease will aid in their diagnosis and ultimately treatment. Additionally, continually monitoring IL-23 could help people with an existing autoimmune disease diagnosis monitor their disease progression and inform any changes in treatment. Synthetic cell receptors like modular extracellular sensor architecture (MESA) are well suited for monitoring biomarkers due to their sensitivity, independence from natural cell signaling pathways, and self-renewal. MESA consists of engineered cell surface receptors that, upon binding a soluble biological target, trigger an internal cell response to produce a fluorescent reporter protein. Therefore, production of fluorescence corresponds to the detection of a target biomolecule above a specific threshold. MESA has been used to monitor soluble biomarkers like interleukin-10 and vascular endothelial growth factor and potentially could be applied to monitor IL-23. I propose to engineer a cell-based sensor of IL-23 using MESA to aid in autoimmune disease detection and monitoring. I plan to 1) incorporate IL-23 specific binders into existing MESA receptors and screen for functional designs, 2) modify the receptor geometry to amplify the output signal-to-noise ratio, and 3) develop a biomaterial encapsulation platform on which to validate MESA sensors in vivo. Preliminary screenings identified at least two viable receptor designs. These novel modifications to MESA will enable continuous, real- time biomolecule observation at a sensitivity unmatched by current methods. When combining cell sensors for IL-23 with existing sensors for interleukin-10 and vascular endothelial growth factor, we will enable multifactorial immune monitoring that will improve patient care and broaden our understanding of autoimmune signaling pathways.