TY - JOUR
T1 - Characterisation of immune cell function in fragment and full-length Huntington's disease mouse models
AU - Träger, Ulrike
AU - Andre, Ralph
AU - Magnusson-Lind, Anna
AU - Miller, James R.C.
AU - Connolly, Colúm
AU - Weiss, Andreas
AU - Grueninger, Stephan
AU - Silajdžić, Edina
AU - Smith, Donna L.
AU - Leavitt, Blair R.
AU - Bates, Gillian P.
AU - Björkqvist, Maria
AU - Tabrizi, Sarah J.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - 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.
AB - 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.
KW - Animal models of disease
KW - Cytokines
KW - Huntington's disease
KW - Innate immune system
KW - Myeloid cells
KW - Neurodegeneration
KW - Neuroinflammation
UR - http://www.scopus.com/inward/record.url?scp=84909609615&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2014.10.012
DO - 10.1016/j.nbd.2014.10.012
M3 - Article
C2 - 25447230
AN - SCOPUS:84909609615
SN - 0969-9961
VL - 73
SP - 388
EP - 398
JO - Neurobiology of disease
JF - Neurobiology of disease
ER -
