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Next-Generation Sequencing Identifies MicroRNAs that Associate with Pathogenic Autoimmune Neuroinflammation in Rats

Bergman, Petra ; James, Tojo ; Kular, Lara ; Ruhrmann, Sabrina ; Kramarova, Tatiana ; Kvist, Anders LU ; Supic, Gordana ; Gillett, Alan ; Pivarcsi, Andor and Jagodic, Maja (2013) In Journal of Immunology 190(8). p.4066-4075
Abstract
MicroRNAs (miRNAs) are known to regulate most biological processes and have been found dysregulated in a variety of diseases, including multiple sclerosis (MS). In this study, we characterized miRNAs that associate with susceptibility to develop experimental autoimmune encephalomyelitis (EAE) in rats, a well-established animal model of MS. Using Illumina next-generation sequencing, we detected 544 miRNAs in the lymph nodes of EAE-susceptible Dark Agouti and EAE-resistant Piebald Virol Glaxo rats during immune activation. Forty-three miRNAs were found differentially expressed between the two strains, with 81% (35 out of 43) showing higher expression in the susceptible strain. Only 33% of tested miRNAs displayed differential expression in... (More)
MicroRNAs (miRNAs) are known to regulate most biological processes and have been found dysregulated in a variety of diseases, including multiple sclerosis (MS). In this study, we characterized miRNAs that associate with susceptibility to develop experimental autoimmune encephalomyelitis (EAE) in rats, a well-established animal model of MS. Using Illumina next-generation sequencing, we detected 544 miRNAs in the lymph nodes of EAE-susceptible Dark Agouti and EAE-resistant Piebald Virol Glaxo rats during immune activation. Forty-three miRNAs were found differentially expressed between the two strains, with 81% (35 out of 43) showing higher expression in the susceptible strain. Only 33% of tested miRNAs displayed differential expression in naive lymph nodes, suggesting that a majority of regulated miRNAs are EAE dependent. Further investigation of a selected six miRNAs indicates differences in cellular source and kinetics of expression. Several of the miRNAs, including miR-146a, miR-21, miR-181a, miR-223, and let-7, have previously been implicated in immune system regulation. Moreover, 77% (33 out of 43) of the miRNAs were associated with MS and other autoimmune diseases. Target genes likely regulated by the miRNAs were identified using computational predictions combined with whole-genome expression data. Differentially expressed miRNAs and their targets involve functions important for MS and EAE, such as immune cell migration through targeting genes like Cxcr3 and cellular maintenance and signaling by regulation of Prkcd and Stat1. In addition, we demonstrated that these three genes are direct targets of miR-181a. Our study highlights the impact of multiple miRNAs, displaying diverse kinetics and cellular sources, on development of pathogenic autoimmune inflammation. The Journal of Immunology, 2013, 190: 4066-4075. (Less)
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author
organization
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type
Contribution to journal
publication status
published
subject
in
Journal of Immunology
volume
190
issue
8
pages
4066 - 4075
publisher
American Association of Immunologists
external identifiers
  • wos:000317274500026
  • scopus:84875994174
  • pmid:23514736
ISSN
1550-6606
DOI
10.4049/jimmunol.1200728
language
English
LU publication?
yes
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b2a19bad-66c8-4b5d-ba9d-0282d5a4eab5 (old id 3739087)
date added to LUP
2016-04-01 13:44:36
date last changed
2019-10-29 02:51:59
@article{b2a19bad-66c8-4b5d-ba9d-0282d5a4eab5,
  abstract     = {MicroRNAs (miRNAs) are known to regulate most biological processes and have been found dysregulated in a variety of diseases, including multiple sclerosis (MS). In this study, we characterized miRNAs that associate with susceptibility to develop experimental autoimmune encephalomyelitis (EAE) in rats, a well-established animal model of MS. Using Illumina next-generation sequencing, we detected 544 miRNAs in the lymph nodes of EAE-susceptible Dark Agouti and EAE-resistant Piebald Virol Glaxo rats during immune activation. Forty-three miRNAs were found differentially expressed between the two strains, with 81% (35 out of 43) showing higher expression in the susceptible strain. Only 33% of tested miRNAs displayed differential expression in naive lymph nodes, suggesting that a majority of regulated miRNAs are EAE dependent. Further investigation of a selected six miRNAs indicates differences in cellular source and kinetics of expression. Several of the miRNAs, including miR-146a, miR-21, miR-181a, miR-223, and let-7, have previously been implicated in immune system regulation. Moreover, 77% (33 out of 43) of the miRNAs were associated with MS and other autoimmune diseases. Target genes likely regulated by the miRNAs were identified using computational predictions combined with whole-genome expression data. Differentially expressed miRNAs and their targets involve functions important for MS and EAE, such as immune cell migration through targeting genes like Cxcr3 and cellular maintenance and signaling by regulation of Prkcd and Stat1. In addition, we demonstrated that these three genes are direct targets of miR-181a. Our study highlights the impact of multiple miRNAs, displaying diverse kinetics and cellular sources, on development of pathogenic autoimmune inflammation. The Journal of Immunology, 2013, 190: 4066-4075.},
  author       = {Bergman, Petra and James, Tojo and Kular, Lara and Ruhrmann, Sabrina and Kramarova, Tatiana and Kvist, Anders and Supic, Gordana and Gillett, Alan and Pivarcsi, Andor and Jagodic, Maja},
  issn         = {1550-6606},
  language     = {eng},
  number       = {8},
  pages        = {4066--4075},
  publisher    = {American Association of Immunologists},
  series       = {Journal of Immunology},
  title        = {Next-Generation Sequencing Identifies MicroRNAs that Associate with Pathogenic Autoimmune Neuroinflammation in Rats},
  url          = {http://dx.doi.org/10.4049/jimmunol.1200728},
  doi          = {10.4049/jimmunol.1200728},
  volume       = {190},
  year         = {2013},
}