BioRxiv
bioRxiv Subject Collection: Systems Biology
This feed contains articles for bioRxiv Subject Collection "Systems Biology"
Temporal perturbation of STAT1/2 activity reveals dynamic ligand discrimination of type I interferon signaling
Type-I interferon (IFN-I) subtypes signal through the same IFNalpha receptor (IFNAR), and initiate temporal STAT1/2 activation to orchestrate innate and adaptive immunity. It remains unknown how IFNAR discriminates between subtypes (e.g., IFNalpha and IFNbeta), and how STAT1/2 signaling is affected by time-varying inputs. Here, we utilize our microfluidic system and live-cell imaging to quantify STAT1/2 activation dynamics in a reporter fibroblast model. Population-averaged and single-cell analyses reveal distinct STAT1/2 responses to various IFNalpha and IFNbeta inputs. Upon continuous stimulation, cells show less sensitivity but more sustained responses to IFNalpha over IFNbeta. A short IFNalpha pulse induces nearly homogeneous STAT1/2 dynamics, in contrast to heterogeneous responses in IFNbeta-pulsed cells. Distinct STAT1/2 refractory states emerge upon exposure to repeated IFN-I pulses, while alternating pulse stimulation reveals that IFNbeta can revoke STAT1/2 refractoriness caused by IFNalpha, but not vice versa. These findings highlight the differences between IFNalpha and IFNbeta signaling and how they can elicit distinct temporal cellular behaviors during viral infection.
Yang, H., van de Kreeke, T., Van Eyndhoven, L. C., Tel, J.
March 28, 2023
http://biorxiv.org/cgi/content/short/2023.03.27.534340v1?rss=1