Final Report Summary - NEUROTRAFFICKING (Molecular mechanisms controlling leukocyte trafficking in the central nervous system)
Cells from the immune system called leukocytes, like holiday travellers, are constantly in motion, trafficking passively over long distances in the blood, locating and entering destination sites in the tissues by using adhesion molecules and receiving activating signals. Once at their destination, cells can migrate through the blood vessel wall into the tissues and potentially engage in contact with resident cells.
Migration of leukocytes across the blood vessel wall in the central nervous system (CNS) represents a critical step in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). It has been previously shown that inhibition of immune cell trafficking in the CNS represents a powerful therapeutic approach in MS patients as well as in EAE. In recent years growing evidence show that immune cells and inflammation mechanisms play an unexpected role in other neurological diseases such as epilepsy.
The main goal of this project was to study the mechanisms controlling immune cell trafficking in neurological diseases such as MS and epilepsy in which inflammation has a detrimental role.
In this project we studied how blood leukocytes, interact with endothelial cells, which are cells that cover the inner part of the vessel wall in the CNS during EAE and epilepsy. We performed in vivo epifluorescence microscopy experiments in inflamed brain venules and identified the molecules controlling the adhesion of Th1 and Th17 cells, which are leukocyte subpopulations playing a key role in the induction of inflammation and autoimmunity. We characterized the differences in the molecular mechanisms controlling the interactions between endothelial cells and Th1 versus Th17 cell at different phases of disease. The results obtained point to new mechanisms controlling leukocyte trafficking in the CNS and novel disease mechanisms. Moreover, the data obtained allowed us to acquire novel methodologies, open new cutting edge research lines and consolidate our group in the field of leukocyte trafficking.
We also used innovative technology such as in vivo two-photon microscopy (TPM) to study the behaviour of leukocytes inside the CNS during EAE and epilepsy. We obtained data suggesting how and when immune cells may play a role in the disease induction and maintenance. We also obtained surprising findings representing inter disciplinary developments, and suggesting that leukocyte trafficking may play a key role not only in MS and epilepsy, but also in other neurological diseases such as Alzheimer's disease. The results obtained generated new fundamental knowledge to the understanding of the role of immune system in neurological disease and opened new avenues for the treatment of human CNS diseases.
The NEUROTRAFFICKING project was particularly successful by: a) achieving all the proposed goals; 2) leading to 17 published papers and several others manuscripts currently in preparation; 3) developing novel experimental methods; 4) inter-disciplinary achievements potentially with high impact on human disease; 5) opening new frontier research lines; 6) consolidating the neuroimmunology group at the University of Verona.
Migration of leukocytes across the blood vessel wall in the central nervous system (CNS) represents a critical step in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). It has been previously shown that inhibition of immune cell trafficking in the CNS represents a powerful therapeutic approach in MS patients as well as in EAE. In recent years growing evidence show that immune cells and inflammation mechanisms play an unexpected role in other neurological diseases such as epilepsy.
The main goal of this project was to study the mechanisms controlling immune cell trafficking in neurological diseases such as MS and epilepsy in which inflammation has a detrimental role.
In this project we studied how blood leukocytes, interact with endothelial cells, which are cells that cover the inner part of the vessel wall in the CNS during EAE and epilepsy. We performed in vivo epifluorescence microscopy experiments in inflamed brain venules and identified the molecules controlling the adhesion of Th1 and Th17 cells, which are leukocyte subpopulations playing a key role in the induction of inflammation and autoimmunity. We characterized the differences in the molecular mechanisms controlling the interactions between endothelial cells and Th1 versus Th17 cell at different phases of disease. The results obtained point to new mechanisms controlling leukocyte trafficking in the CNS and novel disease mechanisms. Moreover, the data obtained allowed us to acquire novel methodologies, open new cutting edge research lines and consolidate our group in the field of leukocyte trafficking.
We also used innovative technology such as in vivo two-photon microscopy (TPM) to study the behaviour of leukocytes inside the CNS during EAE and epilepsy. We obtained data suggesting how and when immune cells may play a role in the disease induction and maintenance. We also obtained surprising findings representing inter disciplinary developments, and suggesting that leukocyte trafficking may play a key role not only in MS and epilepsy, but also in other neurological diseases such as Alzheimer's disease. The results obtained generated new fundamental knowledge to the understanding of the role of immune system in neurological disease and opened new avenues for the treatment of human CNS diseases.
The NEUROTRAFFICKING project was particularly successful by: a) achieving all the proposed goals; 2) leading to 17 published papers and several others manuscripts currently in preparation; 3) developing novel experimental methods; 4) inter-disciplinary achievements potentially with high impact on human disease; 5) opening new frontier research lines; 6) consolidating the neuroimmunology group at the University of Verona.