Research Paper Volume 13, Issue 4 pp 5069—5086

Inhibiting Th1/2 cells influences hepatic capillarization by adjusting sinusoidal endothelial fenestrae through Rho-ROCK-myosin pathway

Yuesi Zhong1, *, , Mingxing Xu1, *, , Jingxiong Hu1, , Xi Huang1, , Nan Lin1, , Meihai Deng1, ,

  • 1 Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, Guangdong, China
* Equal contribution

Received: January 13, 2020       Accepted: November 10, 2020       Published: February 1, 2021
How to Cite

Copyright: © 2021 Zhong et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


CD4+ T cells are considered to be vital in chronic liver diseases, but their exact roles in hepatic capillarization, the typical characteristic of liver fibrosis, are poorly understood. This study aimed to assess the roles of typical subtype of CD4+ T cells, named T helper 1 (Th1) and Th2 cells in liver fibrosis. Taking advantage of well established fibrotic rat model, we conducted in vitro and in vivo experiments to explore the interactions between liver sinusoidal endothelial cells (LSECs) and Th1/2 cells; meanwhile we evaluated the degree of hepatic capillarization when inhibiting these interactions with inhibitory antibodies. Our results showed that prohibiting interactions between Th2 cells and LSECs caused the restoration of fenestrae, increased cytokine level of Th1 cells and reduction of hepatic capillarization; inhibiting the interaction between Th1 cells and LSECs produced the opposite effects. Moreover, increased Rho and myosin light chain phosphorylation were observed when Th1 cells were inhibited with the corresponding inhibitory antibody; Th2 cell inhibition yielded the opposite results. This study indicated that Th1/2 cells steer the capillarization process in different directions and this effect is probably mediated by the Rho-Rho kinase (ROCK)-myosin signaling pathway.


LSECs: liver sinusoidal endothelial cells; Th1: T helper 1; IFN-γ: interferon-γ; IL-4: interleukin-4; ELISA: enzyme-linked immunosorbent assay; SEM: scanning electron microscopy; TEM: transmission electron microscope; p-MLC: phosphorylated myosin light chain; ROCK: Rho associated coiledcoil forming protein kinase; NAFLD: nonalcoholic fatty liver disease; ASH: alcoholic steatohepatitis; NASH: nonalcoholic steatohepatitis; CCl4: carbon tetrachloride; VAP-1: vascular adhesion protein-1; Co-injection: combined injection; NS: normal saline; NC: normal control; vWF: von Willebrand factor; RECA-1: endothelial cell antigen-1; ALT: alanine aminotransferase; AST: aspartate transaminase; HE: haematoxylin-eosin; HSC: hepatic stellate cell; NO: nitric oxide.