T-cell immunoglobulin and mucin ()4 is expressed on APCs, including macrophages, as one of the main amplifiers in the mechanism of liver ischemia-reperfusion injury (IRI) following orthotopic liver transplantation (OLT). Though donor selectively expressed on Kupffer cells serves as a checkpoint regulator of innate immune-driven IRI cascades, its role on cells outside the OLT remains unclear. To dissect the role of donor vs. recipient-specific signaling in IR-induced stress and hepatocellular function, we employed a murine OLT model utilizing -knockout (KO) mice as either donor or recipient (WT → WT, WT → -KO, -KO → WT). In the experimental arm, disruption of donor attenuated IRI-OLT damage, while recipient -null mutation aggravated hepatic IRI concomitant with disturbed lipid metabolism, enhanced endoplasmic reticulum stress, and activated pro-apoptotic signaling in the grafts. In the study, murine hepatocytes co-cultured with -null adipose tissue showed enhanced C/EBP homologous protein (CHOP) expression pattern and susceptibility to hepatocellular death accompanied by activated caspase cascade in response to TNF-α stimulation. In the clinical arm, liver grafts from forty-one transplant patients with enhanced expression showed higher body mass index, augmented hepatic endoplasmic reticulum stress, enhanced pro-apoptotic markers, upregulated innate/adaptive immune responses, exacerbated hepatocellular damage, and inferior graft survival. In conclusion, although is considered a principal villain in peri-transplant early tissue injury, recipient signaling may serve as a savior of IR-triggered metabolic stress in mouse and human OLT recipients.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11235257PMC
http://dx.doi.org/10.3389/frtra.2023.1176384DOI Listing

Publication Analysis

Top Keywords

recipient signaling
8
liver transplantation
8
endoplasmic reticulum
8
reticulum stress
8
stress
5
recipient
4
signaling regulates
4
regulates ischemia
4
ischemia reperfusion-induced
4
reperfusion-induced stress
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!