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- Title
Infiltration of Blood-Derived Monocytes is required for Disease Progress in Experimental Autoimmune Encephalomyelitis (EAE).
- Authors
Ajami, B.; Bennett, J.; Mahdaviani, D.; McNagny, K.; Rossi, F.
- Abstract
Introduction: Microglia, the principal immune cells of the Central Nervous System (CNS), are exquisitely sensitive to CNS injury and disease, fueling a reactive state called microgliosis. We have used parabiosis, a surgical procedure that allows the creation of peripheral blood chimeras without transplantation, to show that unlike most other tissue-resident macrophages that rely on circulating blood-borne precursors for their replacement, microglia are capable of self-renewal within the CNS. In contrast, certain inflammatory pathological conditions such as multiple sclerosis and its murine model, experimental autoimmune encephalomyelitis (EAE), are known to lead to the recruitment of inflammatory monocytes to the CNS. Is the entry of these cells, normally excluded from the CNS, a causal factor in disease progression Methods: To address this question we developed a new experimental model, based on parabiosis and differential bone marrow irradiation, which allows the precise distinction between peripheral blood- derived monocyte/macrophages and resident microglia, thus enabling us to investigate the kinetics of microglia activation, blood born monocytes entry in the CNS and their differentiation into macrophages during EAE progression. Results: Our data reveals a dynamic interplay between macrophages and microglia and strongly supports a causal link between myelomonocytic cell invasion and disease progression. In summary, our data identified the invasion of circulating monocytes into the CNS parenchyma as a major adverse event in EAE progression, supporting therapeutic strategies specifically aimed at inhibiting the migration of myelomonocytic cells rather than that of leukocytes in general.
- Subjects
MONOCYTES; AUTOIMMUNE diseases; ENCEPHALOMYELITIS; CENTRAL nervous system diseases; ANTIGEN presenting cells; AUTOIMMUNITY
- Publication
UBC Medical Journal, 2011, Vol 2, Issue 2, p42
- ISSN
1920-7425
- Publication type
Abstract