The ability of lymphocytes and macrophage-derived cytokines and chemokines to modulate the activation of stromal cells during immune responses is well-documented, but few studies have investigated whether liver myofbroblasts shape the phenotype and function of monocytes in liver disease. In the present study, Kupffer cells were demonstrated to be activated in the inflamed livers of patients with cirrhosis and be in close contact with liver myofbroblasts. The Kupffer cells from cirrhotic livers expressed significantly elevated levels of PD-L1 (also termed B7-H1), TLR4, CD80, CD32 and CD64 relative to those from normal livers. Consistent with this finding, the expression of these surface molecules was significantly upregulated in monocytes following exposure to liver myofbroblasts originating from inflamed livers. Accordingly, the liver myofibroblast-exposed monocytes exhibited a significant increase in dextran endocytosis. These data reveal that bidirectional interactions between liver myofbroblasts and Kupffer cells may function as an 'amplification loop' to enhance infammation further in the liver. Liver myofbro-blasts are central in the pathogenesis of liver diseases and should be considered as targets for the rational design of effective immune-based anti-inflammation therapies. Furthermore, it was also demonstrated that skin fibroblasts were as effective as liver myofbroblasts at inducing monocyte activation, suggesting that fibroblasts, which are numerous in the body, may represent an underrated cell population that is actively involved in immunomodulatory functions.
Zhang, M., Wang, F. L., Zhu, J. Y., Zheng, Y. B., Zhao, Q. Y., Gu, Y. R., … Gao, Z. L. (2013). Liver myofbroblasts regulate the phenotype and function of monocytes through soluble factors in cirrhosis. Experimental and Therapeutic Medicine, 5(1), 143–149. https://doi.org/10.3892/etm.2012.767