학술논문

Inhibition of Toll-like Receptor 4 Using Small Molecule, TAK-242, Protects Islets from Innate Immune Responses.
Document Type
Article
Source
Cells (2073-4409). Mar2024, Vol. 13 Issue 5, p416. 15p.
Subject
*ISLANDS
*SMALL molecules
*IMMUNE response
*LIVER transplantation
*TYPE 1 diabetes
*HEPATIC veins
Language
ISSN
2073-4409
Abstract
Islet transplantation is a therapeutic option to replace β-cell mass lost during type 1 or type 3c diabetes. Innate immune responses, particularly the instant blood-mediated inflammatory reaction and activation of monocytes, play a major role in the loss of transplanted islet tissue. In this study, we aimed to investigate the inhibition of toll-like receptor 4 (TLR4) on innate inflammatory responses. We first demonstrate a significant loss of graft function shortly after transplant through the assessment of miR-375 and miR-200c in plasma as biomarkers. Using in vitro models, we investigate how targeting TLR4 mitigates islet damage and immune cell activation during the peritransplant period. The results of this study support the application of TAK-242 as a therapeutic agent to reduce inflammatory and innate immune responses to islets immediately following transplantation into the hepatic portal vein. Therefore, TLR4 may serve as a target to improve islet transplant outcomes in the future. [ABSTRACT FROM AUTHOR]