| First Author | Kim E | Year | 2021 |
| Journal | Cell Rep | Volume | 37 |
| Issue | 7 | Pages | 110018 |
| PubMed ID | 34788612 | Mgi Jnum | J:322226 |
| Mgi Id | MGI:6883746 | Doi | 10.1016/j.celrep.2021.110018 |
| Citation | Kim E, et al. (2021) TM4SF5-dependent crosstalk between hepatocytes and macrophages to reprogram the inflammatory environment. Cell Rep 37(7):110018 |
| abstractText | Chronic injury to hepatocytes results in inflammation, steatohepatitis, fibrosis, and nonalcoholic fatty liver disease (NAFLD). The tetraspanin TM4SF5 is implicated in fibrosis and cancer. We investigate the role of TM4SF5 in communication between hepatocytes and macrophages (MPhis) and its possible influence on the inflammatory microenvironment that may lead to NAFLD. TM4SF5 induction in differentiated MPhis promotes glucose uptake, glycolysis, and glucose sensitivity, leading to M1-type MPhi activation. Activated M1-type MPhis secrete pro-inflammatory interleukin-6 (IL-6), which induces the secretion of CCL20 and CXCL10 from TM4SF5-positive hepatocytes. Although TM4SF5-dependent secretion of these chemokines enhances glycolysis in M0 MPhis, further chronic exposure reprograms MPhis for an increase in the proportion of M2-type MPhis in the population, which may support diet- and chemical-induced NAFLD progression. We suggest that TM4SF5 expression in MPhis and hepatocytes is critically involved in modulating the inflammatory environment during NAFLD progression. |
