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Differential nerve injury-induced expression of MHC class II in the mouse correlates to genetic variability in the type I promoter of C2ta

Harnesk, Karin; Swanberg, Maria LU ; Diez, Margarita; Olsson, Tomas; Piehl, Fredrik and Lidman, Olle (2009) In Journal of Neuroimmunology 212(1-2). p.44-52
Abstract
Major histocompatibility complex (MHC) class II is of critical importance for the induction of immune responses. Levels of MHC class II in the nervous system are normally low, but expression is up-regulated in many disease conditions. In rat and human, variation in the MHC class II transactivator gene (Uta) is associated with differential expression of MHC class II and susceptibility to autoimmune disease. Here we have characterized the response to facial nerve transection in 7 inbred mouse strains (C57BL/6J, DBA/2J, 129X1/SvJ, BALB/cJ, SJL/J, CBA/J, and NOD). The results demonstrate differences in expression of C2ta and markers for MHC class I and II expression, glial activation. and T cell infiltration. Expression levels of C2ta and Cd74... (More)
Major histocompatibility complex (MHC) class II is of critical importance for the induction of immune responses. Levels of MHC class II in the nervous system are normally low, but expression is up-regulated in many disease conditions. In rat and human, variation in the MHC class II transactivator gene (Uta) is associated with differential expression of MHC class II and susceptibility to autoimmune disease. Here we have characterized the response to facial nerve transection in 7 inbred mouse strains (C57BL/6J, DBA/2J, 129X1/SvJ, BALB/cJ, SJL/J, CBA/J, and NOD). The results demonstrate differences in expression of C2ta and markers for MHC class I and II expression, glial activation. and T cell infiltration. Expression levels of C2ta and Cd74 followed similar patterns, in contrast to MHC class I and markers of glial activation. The regulatory region of the C2ta gene was subsequently sequenced in the four strains (C57BL/6/J, DBA/2J, SJL/J and 129X1/SvJ) that represented the phenotypical extremes with regard to C2ta/Cd74 expression. We found 3 single nucleotide polymorphisms in the type I (pI) and type III (pIII) promoters of C2ta, respectively. Higher expression of pI in 129X1/SvJ correlated with the pI haplotype specific for this strain. Furthermore, congenic strains carrying the 129X1/SvJ C2ta allele on B6 background displayed significantly higher C2ta and Cd74 expression compared to parental controls. We conclude that genetic polymorphisms in the type I promoter of C2ta regulates differential expression of MHC class II, but not MHC class I, Cd3 and other markers of glial activation. (C) 2009 Elsevier B.V. All rights reserved. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
regulation, Genetic, Polymorphism, Inflammation, MHC, Microglia, Nerve injury
in
Journal of Neuroimmunology
volume
212
issue
1-2
pages
44 - 52
publisher
Elsevier
external identifiers
  • wos:000268650400006
  • scopus:67649970511
ISSN
1872-8421
DOI
10.1016/j.jneuroim.2009.04.019
language
English
LU publication?
yes
id
375838aa-a97e-401d-884a-e685ad9a32db (old id 1459904)
date added to LUP
2009-08-31 10:53:06
date last changed
2017-03-26 03:30:24
@article{375838aa-a97e-401d-884a-e685ad9a32db,
  abstract     = {Major histocompatibility complex (MHC) class II is of critical importance for the induction of immune responses. Levels of MHC class II in the nervous system are normally low, but expression is up-regulated in many disease conditions. In rat and human, variation in the MHC class II transactivator gene (Uta) is associated with differential expression of MHC class II and susceptibility to autoimmune disease. Here we have characterized the response to facial nerve transection in 7 inbred mouse strains (C57BL/6J, DBA/2J, 129X1/SvJ, BALB/cJ, SJL/J, CBA/J, and NOD). The results demonstrate differences in expression of C2ta and markers for MHC class I and II expression, glial activation. and T cell infiltration. Expression levels of C2ta and Cd74 followed similar patterns, in contrast to MHC class I and markers of glial activation. The regulatory region of the C2ta gene was subsequently sequenced in the four strains (C57BL/6/J, DBA/2J, SJL/J and 129X1/SvJ) that represented the phenotypical extremes with regard to C2ta/Cd74 expression. We found 3 single nucleotide polymorphisms in the type I (pI) and type III (pIII) promoters of C2ta, respectively. Higher expression of pI in 129X1/SvJ correlated with the pI haplotype specific for this strain. Furthermore, congenic strains carrying the 129X1/SvJ C2ta allele on B6 background displayed significantly higher C2ta and Cd74 expression compared to parental controls. We conclude that genetic polymorphisms in the type I promoter of C2ta regulates differential expression of MHC class II, but not MHC class I, Cd3 and other markers of glial activation. (C) 2009 Elsevier B.V. All rights reserved.},
  author       = {Harnesk, Karin and Swanberg, Maria and Diez, Margarita and Olsson, Tomas and Piehl, Fredrik and Lidman, Olle},
  issn         = {1872-8421},
  keyword      = {regulation,Genetic,Polymorphism,Inflammation,MHC,Microglia,Nerve injury},
  language     = {eng},
  number       = {1-2},
  pages        = {44--52},
  publisher    = {Elsevier},
  series       = {Journal of Neuroimmunology},
  title        = {Differential nerve injury-induced expression of MHC class II in the mouse correlates to genetic variability in the type I promoter of C2ta},
  url          = {http://dx.doi.org/10.1016/j.jneuroim.2009.04.019},
  volume       = {212},
  year         = {2009},
}