Current liver research: T-cell activationin immune-mediated hepatic inflammation is controlled by CEACAM1
Many liver diseases, such as autoimmune hepatitis and primary sclerosing cholangitis, are triggered by T cells, can become chronic and lead to the destruction of the liver (tissue degeneration and fibrosis). T cells carrying the special surface molecule CD4 cause immune-mediated liver damage – there is an imbalance between the so-called regulatory T cells (Treg, anti-inflammatory) and the conventional T cells (Tkonv, inflammatory). The working group around PD Dr. Andrea K. Horst and Prof. Dr. Gisa Tiegs (project leader of the SFB841 subproject B01) has succeeded in demonstrating the regulation of the activation of T cells by the Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1).
This protein is a co-receptor that, in its short form, causes T cells to be activated and the anti-inflammatory regulatory T cells to be formed. In contrast, formation of the long form of CEACAM1 leads to inactivation of T cells. So far, an antifibrotic effect in the liver has been demonstrated for CEACAM1, in the context of immune-mediated hepatitis the role of CEACAM1 has been unclear. In a model with CD4 + T-cell mediated hepatic inflammation in which no CECAM1 can be formed, it was observed that T cells were unable to develop into regulatory T cells during ongoing hepatic inflammation.
Furthermore, it has been demonstrated that the short form of CEACAM1 in CD4 + T cells enhances the production of key messengers such as interleukin 2 and the signal molecule STAT5, thus improving the induction and stability of regulatory T cells, thus protecting against T cell induced liver damage works.