Macrophages, a particular type of white blood cell, can act in two distinct ways. They might be triggered by a pathogen and release proteins that encourage inflammation. In other situations, tissue in our body might instead signal for macrophages to tamp down inflammation. This dynamic role is known as macrophage polarization, and it is crucial to the body’s response to wounds, cancer, and autoimmune conditions.

A team led by Professor Elizabeth Wayne has introduced a new way to measure macrophage polarization by tracking the STAT6 signaling protein. They modified human cells to produce STAT6 with a fluorescent protein, then tracked it using bioluminescence temporal spectrometry. Dysregulation of the STAT6 pathway is seen in several forms of lymphoma, tumors in the body’s connective tissues, asthma, and food allergies.

Results were published in June in Cell Systems. Professor Jennifer Davis, Director of UW’s  Institute for Stem Cell and Regenerative Medicine, and colleagues at Carnegie Mellon University, University of Tennessee, and Oak Ridge National Laboratory also contributed to the work. It was supported by a Maximizing Investigators’ Research Award, or R35 grant, from the National Institute of General Medical Sciences.

Most tools used to study macrophage polarization currently capture a single measure of STAT6 levels in a single moment. The new method from the Wayne team, however, shows the STAT6 levels as they rise and fall over time.

With the ability to see the signalling protein’s activity in real time, the team then built a model that shows when and how strongly the cells are shifting from encouraging to discouraging inflammation. This method provides an unprecedented view of how STAT6’s behavior influences what role macrophages will take.

“By pairing a non-invasive longitudinal readout with a model of the biology driving that activity, we’ve built an integrated platform that reveals the mechanisms underlying macrophage polarization,” Wayne said.

“Macrophage polarization impacts many immune functions, so ultimately our method could be used to improve therapies for a broad set of issues like autoimmune conditions, cancer, and wound care.”

Wayne has used bioluminescence spectronomy in previous research as well, including a study of how monocytes differentiate into macrophages that appeared in the 2025 Young Innovators issue of Cellular and Molecular Bioengineering.