Mattke Jordan, Darden Carly M, Vasu Srividya, Lawrence Michael C, Kirkland Jeffrey, Kane Robert R, Naziruddin Bashoo
Institute of Biomedical Studies, Baylor University, Waco, TX 76706, USA.
Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX 75204, USA.
Cells. 2024 Feb 27;13(5):416. doi: 10.3390/cells13050416.
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.
胰岛移植是一种治疗选择，用于替代1型或3c型糖尿病期间丢失的β细胞量。固有免疫反应，特别是即时血液介导的炎症反应和单核细胞的激活，在移植胰岛组织的丢失中起主要作用。在本研究中，我们旨在研究 toll 样受体4（TLR4）对固有炎症反应的抑制作用。我们首先通过评估血浆中的miR-375和miR-200c作为生物标志物，证明移植后不久移植物功能有显著丧失。使用体外模型，我们研究靶向TLR4如何减轻移植期间胰岛损伤和免疫细胞激活。本研究结果支持将TAK-242作为一种治疗药物应用，以减少移植到肝门静脉后立即对胰岛的炎症和固有免疫反应。因此，TLR4未来可能作为改善胰岛移植结果的一个靶点。
