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Document Version Version Comment Date Status
442942.0 Automatic journal name synchronization 23.01.2010 20:15 Released

ID: 442942.0, MPI für Neurobiologie / Neuroimmunology
MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47
Authors:Junker, A.; Krumbholz, M.; Eisele, S.; Mohan, H.; Augstein, F.; Bittner, R.; Lassmann, H.; Wekerle, H.; Hohlfeld, R.; Meinl, E.
Date of Publication (YYYY-MM-DD):2009-12
Title of Journal:Brain
Journal Abbrev.:Brain
Start Page:3342
End Page:3352
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:We established microRNA profiles from active and inactive multiple sclerosis lesions. Using laser capture microdissection from multiple sclerosis lesions to pool single cells and in vitro cultures, we assigned differentially expressed microRNA to specific cell types. Astrocytes contained all 10 microRNA that were most strongly upregulated in active multiple sclerosis lesions, including microRNA-155, which is known to modulate immune responses in different ways but so far had not been assigned to central nervous system resident cells. MicroRNA-155 was expressed in human astrocytes in situ, and further induced with cytokines in human astrocytes in vitro. This was confirmed with astrocyte cultures from microRNA-155-|-lacZ mice. We matched microRNA upregulated in phagocytically active multiple sclerosis lesions with downregulated protein coding transcripts. This converged on CD47, which functions as a 'don't eat me' signal inhibiting macrophage activity. Three microRNA upregulated in active multiple sclerosis lesions (microRNA-34a, microRNA-155 and microRNA-326) targeted the 3'-untranslated region of CD47 in reporter assays, with microRNA-155 even at two distinct sites. Our findings suggest that microRNA dysregulated in multiple sclerosis lesions reduce CD47 in brain resident cells, releasing macrophages from inhibitory control, thereby promoting phagocytosis of myelin. This mechanism may have broad implications for microRNA-regulated macrophage activation in inflammatory diseases.
Free Keywords:multiple sclerosis; microRNAs; CD47; autoimmunity; inflammation
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Affiliations:MPI für Neurobiologie/Neuroimmunology (Wekerle)
MPI für Neurobiologie/Neuroimmunology (Wekerle)/Clinical Neuroimmunology (Hohlfeld)
External Affiliations:[Lassmann, Hans] Med Univ Vienna, Ctr Brain Res, Vienna, Austria.
Identifiers:ISI:000272926200020 [ID No:1]
ISSN:0006-8950 [ID No:2]