miR-143 Regulates Memory T Cell Differentiation by Reprogramming T Cell Metabolism
Abstract
MicroRNAs are an important regulator for T cell immune response. In this study, we aimed to identify microRNAs with the potential to regulate T cell differentiation. The influence of miR-143 on differentiation and function of CD8+ T cells from healthy donors were detected, and it was found that miR-143 overexpression could significantly increase the differentiation of central memory T (Tcm) CD8+ cells, decrease cell apoptosis, and increase proinflammatory cytokine secretion. Furthermore, the specific killing of HER2-CAR T cells against esophageal cancer cell line TE-7 was enhanced by miR-143 overexpression. Glucose transporter 1 (Glut-1) was identified as the critical target gene of miR-143 in the role of T cell regulation. By inhibition Glut-1, miR-143 inhibited glucose uptake and glycolysis in T cell to regulated T cell differentiation. Tcm cell populations were also suppressed in parallel with the downregulation of miR-143 in tumor tissues from 13 patients with esophagus cancer. IDO and its metabolite kynurenine in the tumor microenvironment were screened as an upstream regulator of miR-143. IDO small interfering RNA significantly increased the expression of miR-143 and Tcm cell population. In conclusion, our results show th...Continue Reading
References
Citations
Related Concepts
Related Feeds
Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis
Cancer Metabolism
In order for cancer cells to maintain rapid, uncontrolled cell proliferation, they must acquire a source of energy. Cancer cells acquire metabolic energy from their surrounding environment and utilize the host cell nutrients to do so. Here is the latest research on cancer metabolism.
Apoptosis in Cancer
Apoptosis is an important mechanism in cancer. By evading apoptosis, tumors can continue to grow without regulation and metastasize systemically. Many therapies are evaluating the use of pro-apoptotic activation to eliminate cancer growth. Here is the latest research on apoptosis in cancer.