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Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.

Träger, Ulrike; Andre, Ralph; Magnusson-Lind, Anna LU ; Miller, James R C; Connolly, Colúm; Weiss, Andreas; Grueninger, Stephan; Silajdzic, Edina LU ; Smith, Donna L and Leavitt, Blair R, et al. (2015) In Neurobiology of Disease 73. p.388-398
Abstract
Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsive to immune stimuli. Several mouse models of HD also show elevated plasma levels of inflammatory cytokines. To further determine the degree to which these models recapitulate observations in HD patients, we evaluated various myeloid cell populations from different HD mouse models to determine whether they are similarly hyper-responsive, as well as measuring other aspects of myeloid cell function. Myeloid cells from each of the... (More)
Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsive to immune stimuli. Several mouse models of HD also show elevated plasma levels of inflammatory cytokines. To further determine the degree to which these models recapitulate observations in HD patients, we evaluated various myeloid cell populations from different HD mouse models to determine whether they are similarly hyper-responsive, as well as measuring other aspects of myeloid cell function. Myeloid cells from each of the three mouse models studied, R6/2, HdhQ150 knock-in and YAC128, showed increased cytokine production when stimulated. However, bone marrow CD11b(+) cells did not show the same hyper-responsive phenotype as spleen and blood cells. Furthermore, macrophages isolated from R6/2 mice show increased levels of phagocytosis, similar to findings in HD patients. Taken together, these results show significant promise for these mouse models to be used to study targeting innate immune pathways identified in human cells, thereby helping to understand the role the peripheral immune system plays in HD progression. (Less)
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Neurobiology of Disease
volume
73
pages
388 - 398
publisher
Elsevier
external identifiers
  • pmid:25447230
  • wos:000346328100036
  • scopus:84909609615
ISSN
0969-9961
DOI
10.1016/j.nbd.2014.10.012
language
English
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yes
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f63ea4ce-594f-4d57-ad8a-bc1545e43b65 (old id 4913364)
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http://www.ncbi.nlm.nih.gov/pubmed/25447230?dopt=Abstract
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2015-01-08 15:12:24
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2017-11-12 03:11:29
@article{f63ea4ce-594f-4d57-ad8a-bc1545e43b65,
  abstract     = {Inflammation is a growing area of research in neurodegeneration. In Huntington's disease (HD), a fatal inherited neurodegenerative disease caused by a CAG-repeat expansion in the gene encoding huntingtin, patients have increased plasma levels of inflammatory cytokines and circulating monocytes that are hyper-responsive to immune stimuli. Several mouse models of HD also show elevated plasma levels of inflammatory cytokines. To further determine the degree to which these models recapitulate observations in HD patients, we evaluated various myeloid cell populations from different HD mouse models to determine whether they are similarly hyper-responsive, as well as measuring other aspects of myeloid cell function. Myeloid cells from each of the three mouse models studied, R6/2, HdhQ150 knock-in and YAC128, showed increased cytokine production when stimulated. However, bone marrow CD11b(+) cells did not show the same hyper-responsive phenotype as spleen and blood cells. Furthermore, macrophages isolated from R6/2 mice show increased levels of phagocytosis, similar to findings in HD patients. Taken together, these results show significant promise for these mouse models to be used to study targeting innate immune pathways identified in human cells, thereby helping to understand the role the peripheral immune system plays in HD progression.},
  author       = {Träger, Ulrike and Andre, Ralph and Magnusson-Lind, Anna and Miller, James R C and Connolly, Colúm and Weiss, Andreas and Grueninger, Stephan and Silajdzic, Edina and Smith, Donna L and Leavitt, Blair R and Bates, Gillian P and Björkqvist, Maria and Tabrizi, Sarah J},
  issn         = {0969-9961},
  language     = {eng},
  pages        = {388--398},
  publisher    = {Elsevier},
  series       = {Neurobiology of Disease},
  title        = {Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models.},
  url          = {http://dx.doi.org/10.1016/j.nbd.2014.10.012},
  volume       = {73},
  year         = {2015},
}