Research Team Prof. Dr. med. Ingo Bechmann
Many antigens (grafts/viruses) eliciting strong immune reactions elsewhere in the body are tolerated within the eye and the brain. From an evolutionary point of view, this immune privilege may reflect the need for the immune system to act particularly careful at sites of poor regenerative capacity. The maintenance of Herpes zoster is a good example for this interpretation. Apparently, it is better for the individual to live with certain neurotropic viruses than to loose all infected neurons.
Upon peripheral immunization with an antigen previously tolerated within the brain, immune tolerance breaks down showing that epitopes in the brain “cannot elicit, but succumb to an immune reaction” (Medawar 1948).
Our group is interested in the mechanisms maintaining and breaking immune tolerance within the brain. Within this framework, the pathogenesis of multiple sclerosis (MS) is a strong focus. Some key questions are:
1. How are immune cells adopted to the local environment of the brain?
Priller J, Flugel A, Wehner T, Boentert M, Haas CA, Prinz M, Fernandez-Klett F, Prass K, Bechmann I, de Boer BA, Frotscher M, Kreutzberg GW, Persons DA, Dirnagl U (2001) Targeting gene-modified hematopoietic cells to the central nervous system: use of green fluorescent protein uncovers microglial engraftment. Nat Med 7(12):1356-1361.
Bechmann I, Goldmann J, Kovac AD, Kwidzinski E, Simburger E, Naftolin F, Dirnagl U, Nitsch R, Priller J (2005) Circulating monocytic cells infiltrate layers of anterograde axonal degeneration where they transform into microglia. FASEB J 19(6):647-649
Kwidzinski E, Bunse J, Aktas O, Richter D, Mutlu L, Zipp F, Nitsch R, Bechmann I (2005) Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation. FASEB J 19(10):1347-1349
2. How is tissue damage induced during neuroinflammation?
Aktas O, Smorodchenko A, Brocke S, Infante-Duarte C, Topphoff US, Vogt J, Prozorovski T, Meier S, Osmanova V, Pohl E, Bechmann I, Nitsch R, Zipp F (2005) Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 46(3):421-432
Nitsch R*, Bechmann I*, Deisz RA, Haas D, Lehmann TN, Wendling U, Zipp F (2000) Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) Lancet 356(9232):827-828
3. What enables immune cells to migrate to sites of damage?
Rappert A*, Bechmann I*, Pivneva T, Mahlo J, Biber K, Nolte C, Kovac AD, Gerard C, Boddeke HW, Nitsch R, Kettenmann H (2005) CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion. J Neurosci 24(39):8500-8509
Bermpohl D, Halle A, Freyer D, Dagand E, Braun JS, Bechmann I, Schroder NW, Weber JR (2005) Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways. J Clin Invest 115(6):1607-1615
Bechmann I, Galea I, Perry H (2007) What is the blood-brain barrier (not). Trends Immunol. 28(1)
4. Are brain antigens transported to lymphoid organs by brain antigen-presenting cells? Which routes do these cells take and what enables them to leave the tissue?
Goldmann J, Kwidzinski E, Brandt C, Mahlo J, Richter D, Bechmann I (2006) T cells traffic from brain to cervical lymph nodes via the cribroid plate and the nasal mucosa. J Leukoc Biol 80(4):797-801
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