Capturing the dynamics of STAT6 macrophage polarization using bioluminescence temporal signatures

Journal article

Shiyuan Zheng, Yi-Hsuan Chiang, Dasia Aldarondo, Alexandra Locke, Jagadambika Gunaje, Jennifer Davis, Zachary R. Fox, Belinda S. Akpa, Elizabeth Wayne
Cell Systems, 2026, p. 101643

DOI: 10.1016/j.cels.2026.101643

Cite

APA Click to copy
Zheng, S., Chiang, Y.-H., Aldarondo, D., Locke, A., Gunaje, J., Davis, J., … Wayne, E. (2026). Capturing the dynamics of STAT6 macrophage polarization using bioluminescence temporal signatures. Cell Systems, 101643. https://doi.org/10.1016/j.cels.2026.101643

Chicago/Turabian Click to copy
Zheng, Shiyuan, Yi-Hsuan Chiang, Dasia Aldarondo, Alexandra Locke, Jagadambika Gunaje, Jennifer Davis, Zachary R. Fox, Belinda S. Akpa, and Elizabeth Wayne. “Capturing the Dynamics of STAT6 Macrophage Polarization Using Bioluminescence Temporal Signatures.” Cell Systems (2026): 101643.

MLA Click to copy
Zheng, Shiyuan, et al. “Capturing the Dynamics of STAT6 Macrophage Polarization Using Bioluminescence Temporal Signatures.” Cell Systems, 2026, p. 101643, doi:10.1016/j.cels.2026.101643.

BibTeX Click to copy

@article{zheng2026a,
  title = {Capturing the dynamics of STAT6 macrophage polarization using bioluminescence temporal signatures},
  year = {2026},
  journal = {Cell Systems},
  pages = {101643},
  doi = {10.1016/j.cels.2026.101643},
  author = {Zheng, Shiyuan and Chiang, Yi-Hsuan and Aldarondo, Dasia and Locke, Alexandra and Gunaje, Jagadambika and Davis, Jennifer and Fox, Zachary R. and Akpa, Belinda S. and Wayne, Elizabeth}
}

Abstract

Signal transducer and activator of transcription 6 (STAT6) signaling is activated by interleukin 4 (IL-4) and IL-13 and drives alternative macrophage polarization, which is pivotal in wound healing, immunosuppression, and tumor progression. STAT6 functions by forming a phosphorylated homodimer and binding to STAT6-responsive promoter elements to regulate anti-inflammatory genes. Measuring STAT6 activity can serve as a proxy for assessing macrophage polarization. We developed a STAT6-responsive-element (RE) THP-1 reporter to assess STAT6 activation in response to inflammatory stimuli. We quantitatively measured macrophage polarization by using bioluminescence temporal spectrometry (BTS). Human THP-1 monocytes were transduced with lentivirus to express STAT6-RE-firefly luciferase (FLuc)-green fluorescent protein (GFP). The STAT6-RE accurately reported endogenous STAT6 activity, as confirmed by ELISA, western blotting, bioluminescence, and imaging techniques. We developed a systems model to connect emergent bioluminescence to the kinetics of relevant STAT6 cellular signaling events. These results indicate a probe for assessing macrophage alternative polarization, enhancing our understanding of the relationship between molecular mechanisms and macrophage polarization.