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  MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47

Junker, A., Krumbholz, M., Eisele, S., Mohan, H., Augstein, F., Bittner, R., et al. (2009). MicroRNA profiling of multiple sclerosis lesions identifies modulators of the regulatory protein CD47. Brain, 132, 3342-3352.

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 Creators:
Junker, A.1, Author           
Krumbholz, M.1, Author           
Eisele, S.1, Author           
Mohan, H.1, Author           
Augstein, F.1, Author           
Bittner, R.1, Author           
Lassmann, H.2, Author
Wekerle, H.1, Author           
Hohlfeld, R.1, Author           
Meinl, E.1, Author           
Affiliations:
1Department: Neuroimmunology / Wekerle, MPI of Neurobiology, Max Planck Society, ou_1113547              
2[Lassmann, Hans] Med Univ Vienna, Ctr Brain Res, Vienna, Austria., ou_persistent22              

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Free keywords: multiple sclerosis; microRNAs; CD47; autoimmunity; inflammation
 Abstract: 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.

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Language(s): eng - English
 Dates: 2009-12
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 442942
ISI: 000272926200020
 Degree: -

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Title: Brain
  Alternative Title : Brain
Source Genre: Journal
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Publ. Info: -
Pages: - Volume / Issue: 132 Sequence Number: - Start / End Page: 3342 - 3352 Identifier: ISSN: 0006-8950