Article: Antigen presenting cell abnormalities in the Cln3(-/-) mouse model of juvenile neuronal ceroid lipofuscinosis.
2016 Volume 1862, Issue 7, Page(s) 1324–1336
Abstract: Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in ... ...
| Abstract | Mutations of the CLN3 gene lead to juvenile neuronal ceroid lipofuscinosis (JNCL), an autosomal recessive lysosomal storage disorder that causes progressive neurodegeneration in children and adolescents. There is evidence of immune system involvement in pathology that has been only minimally investigated. We characterized bone marrow stem cell-derived antigen presenting cells (APCs), peritoneal macrophages, and leukocytes from spleen and blood, harvested from the Cln3(-/-) mouse model of JNCL. We detected dramatically elevated CD11c surface levels and increased total CD11c protein in Cln3(-/-) cell samples compared to wild type. This phenotype was specific to APCs and also to a loss of CLN3, as surface levels did not differ from wild type in other leukocyte subtypes nor in cells from two other NCL mouse models. Subcellularly, CD11c was localized to lipid rafts, indicating that perturbation of surface levels is attributable to derangement of raft dynamics, which has previously been shown in Cln3 mutant cells. Interrogation of APC function revealed that Cln3(-/-) cells have increased adhesiveness to CD11c ligands as well as an abnormal secretory pattern that closely mimics what has been previously reported for Cln3 mutant microglia. Our results show that CLN3 deficiency alters APCs, which can be a major contributor to the autoimmune response in JNCL. |
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| MeSH term(s) | Animals ; Antigen-Presenting Cells/immunology ; Antigen-Presenting Cells/pathology ; Autoimmunity ; CD11c Antigen/analysis ; CD11c Antigen/immunology ; Cells, Cultured ; Cytokines/immunology ; Disease Models, Animal ; Gene Deletion ; Leukocytes/immunology ; Leukocytes/pathology ; Macrophages/immunology ; Macrophages/pathology ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/immunology ; Mice, Inbred C57BL ; Molecular Chaperones/genetics ; Molecular Chaperones/immunology ; Neuronal Ceroid-Lipofuscinoses/genetics ; Neuronal Ceroid-Lipofuscinoses/immunology ; Neuronal Ceroid-Lipofuscinoses/pathology |
| Chemical Substances | CD11c Antigen ; CLN3 protein, mouse ; Cytokines ; Membrane Glycoproteins ; Molecular Chaperones |
| Language | English |
| Publishing date | 2016-04-19 |
| Publishing country | Netherlands |
| Document type | Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't |
| ZDB-ID | 60-7 |
| ISSN | 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399 |
| ISSN (online) | 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 |
| ISSN | 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399 |
| DOI | 10.1016/j.bbadis.2016.04.011 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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