Therapeutic targeting of T cell migration during hepatic ischemia-reperfusion

• Applicant: Professor Dr. Andrej Khandoga
• Subject Area: Gastroenterology
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 223989552

T cells play a critical role during hepatic ischemia-reperfusion (I/R). The exact mechanisms that control CD4+ T cell migration during alloantigen-independent postischemic inflammation remains unclear. The central aims of the proposed project are therefore as follows: 1) to address the mechanisms and the pathophysiological role of T cell migration in the postischemic hepatic microcirculation and 2) to develop new therapeutic strategies to prevent postischemic injury by affecting the single steps of T cell trafficking from blood through the vessel wall into the parenchyma. In mice, we will test the following hypotheses using intravital microscopic techniques in combination with molecular biological methods: (I) Inhibition of protease-activated receptor-4 reduces CD4+T cell intravascular recruitment via attenuation of platelet- and endothelial cell activation. (II) Adhesion receptor CD99 alone or in cooperation with PECAM-1 mediates transendothelial migration of T cells. (III) T cells migrating into the liver parenchyma interact with hepatic stellate cells directly; such interaction is an important mechanism regulating induction of liver injury, regeneration as well as fibrogenesis after I/R.

• DFG Programme: Research Grants