Deans' stroke musings: STING deficiency alleviates ischemia–reperfusion injury via JAK2/STAT3-mediated macrophage polarization and autophagy

Changing stroke rehab and research worldwide now.Time is Brain! trillions and trillions of neurons that DIE each day because there are NO effective hyperacute therapies besides tPA(only 12% effective). I have 523 posts on hyperacute therapy, enough for researchers to spend decades proving them out. These are my personal ideas and blog on stroke rehabilitation and stroke research. Do not attempt any of these without checking with your medical provider. Unless you join me in agitating, when you need these therapies they won't be there.

What this blog is for:

My blog is not to help survivors recover, it is to have the 10 million yearly stroke survivors light fires underneath their doctors, stroke hospitals and stroke researchers to get stroke solved. 100% recovery. The stroke medical world is completely failing at that goal, they don't even have it as a goal. Shortly after getting out of the hospital and getting NO information on the process or protocols of stroke rehabilitation and recovery I started searching on the internet and found that no other survivor received useful information. This is an attempt to cover all stroke rehabilitation information that should be readily available to survivors so they can talk with informed knowledge to their medical staff. It lays out what needs to be done to get stroke survivors closer to 100% recovery. It's quite disgusting that this information is not available from every stroke association and doctors group.

Tuesday, December 2, 2025

STING deficiency alleviates ischemia–reperfusion injury via JAK2/STAT3-mediated macrophage polarization and autophagy

Ask your competent? doctor what protocol will be created to get survivors better recovery. Oh no, your incompetent? doctor either can't or won't do that? Fire them!

STING deficiency alleviates ischemia–reperfusion injury via JAK2/STAT3-mediated macrophage polarization and autophagy

https://doi.org/10.1016/j.intimp.2025.115784 Get rights and content

Highlights

•
STING and JAK2/STAT3 pathways are activated during IIR injury.
•
STING promotes M1 macrophage polarization and enhances autophagy.
•
IFN-γ via STING triggers TNF-α and IL-6 through JAK2/STAT3 signaling.
•
STING is a potential therapeutic target for intestinal IIR-related inflammation.

Abstract

Intestinal ischemia–reperfusion (IIR) injury triggers severe inflammation and epithelial barrier damage, often leading to systemic complications. The stimulator of interferon genes (STING), a key regulator of innate immunity, has been implicated in inflammatory responses, but its role in IIR remains unclear. This study aimed to determine whether STING influences intestinal injury through macrophage polarization and autophagy regulation via the JAK2/STAT3 signaling pathway. Our results showed that IIR induced STING expression, promoted interferon-gamma (IFN-γ) production, activated JAK2/STAT3 signaling, and drove M1 macrophage polarization. Inhibition or deletion of STING suppressed JAK2/STAT3 activation, shifted macrophage polarization toward the anti-inflammatory M2 phenotype, enhanced autophagy, and alleviated epithelial damage. These effects were reproduced with JAK2 inhibition. Conversely, blocking autophagy reversed the protective effects, suggesting that autophagy plays a crucial role in this process. Our study indicates that STING aggravates IIR injury by promoting IFN-γ–mediated JAK2/STAT3 activation, M1 macrophage polarization, and autophagy dysregulation. Targeting STING may offer a novel therapeutic strategy for mitigating intestinal ischemia–reperfusion injury.

Graphical abstract

Intestinal ischemia-reperfusion injury induces dsDNA release from intestinal epithelial cells, activating the cGAS–STING–NF-κB pathway, upregulating IFN-γ, and promoting M1 polarization and JAK2–STAT3–mediated autophagy, thereby exacerbating epithelial injury. IEC: Intestinal epithelial cells, Mφ: macrophage.