iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice
Huntington’s disease (HD) is an inherited neurodegenerative disorder which is caused by a mutation of the huntingtin (HTT) gene. Although the pathogenesis of HD has been associated with inflammatory responses, if and how the immune system contributes to the onset of HD is largely unknown. Invariant...
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| Format: | Article |
| Language: | English |
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Wiley
2019-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2019/3540974 |
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| _version_ | 1850219716193288192 |
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| author | Hyun Jung Park Sung Won Lee Wooseok Im Manho Kim Luc Van Kaer Seokmann Hong |
| author_facet | Hyun Jung Park Sung Won Lee Wooseok Im Manho Kim Luc Van Kaer Seokmann Hong |
| author_sort | Hyun Jung Park |
| collection | DOAJ |
| description | Huntington’s disease (HD) is an inherited neurodegenerative disorder which is caused by a mutation of the huntingtin (HTT) gene. Although the pathogenesis of HD has been associated with inflammatory responses, if and how the immune system contributes to the onset of HD is largely unknown. Invariant natural killer T (iNKT) cells are a group of innate-like regulatory T lymphocytes that can rapidly produce various cytokines such as IFNγ and IL4 upon stimulation with the glycolipid α-galactosylceramide (α-GalCer). By employing both R6/2 Tg mice (murine HD model) and Jα18 KO mice (deficient in iNKT cells), we investigated whether alterations of iNKT cells affect the development of HD in R6/2 Tg mice. We found that Jα18 KO R6/2 Tg mice showed disease progression comparable to R6/2 Tg mice, indicating that the absence of iNKT cells did not have any significant effects on HD development. However, repeated activation of iNKT cells with α-GalCer facilitated HD progression in R6/2 Tg mice, and this was associated with increased infiltration of iNKT cells in the brain. Taken together, our results demonstrate that repeated α-GalCer treatment of R6/2 Tg mice accelerates HD progression, suggesting that immune activation can affect the severity of HD pathogenesis. |
| format | Article |
| id | doaj-art-799263a2bce44cf49ab5f3a96dcbeeff |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2019-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-799263a2bce44cf49ab5f3a96dcbeeff2025-08-20T02:07:17ZengWileyMediators of Inflammation0962-93511466-18612019-01-01201910.1155/2019/35409743540974iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic MiceHyun Jung Park0Sung Won Lee1Wooseok Im2Manho Kim3Luc Van Kaer4Seokmann Hong5Department of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaDepartment of Neurology, Seoul National University Hospital, Seoul 03080, Republic of KoreaDepartment of Neurology, Seoul National University Hospital, Seoul 03080, Republic of KoreaDepartment of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USADepartment of Integrative Bioscience and Biotechnology, Institute of Anticancer Medicine Development, Sejong University, Seoul 05006, Republic of KoreaHuntington’s disease (HD) is an inherited neurodegenerative disorder which is caused by a mutation of the huntingtin (HTT) gene. Although the pathogenesis of HD has been associated with inflammatory responses, if and how the immune system contributes to the onset of HD is largely unknown. Invariant natural killer T (iNKT) cells are a group of innate-like regulatory T lymphocytes that can rapidly produce various cytokines such as IFNγ and IL4 upon stimulation with the glycolipid α-galactosylceramide (α-GalCer). By employing both R6/2 Tg mice (murine HD model) and Jα18 KO mice (deficient in iNKT cells), we investigated whether alterations of iNKT cells affect the development of HD in R6/2 Tg mice. We found that Jα18 KO R6/2 Tg mice showed disease progression comparable to R6/2 Tg mice, indicating that the absence of iNKT cells did not have any significant effects on HD development. However, repeated activation of iNKT cells with α-GalCer facilitated HD progression in R6/2 Tg mice, and this was associated with increased infiltration of iNKT cells in the brain. Taken together, our results demonstrate that repeated α-GalCer treatment of R6/2 Tg mice accelerates HD progression, suggesting that immune activation can affect the severity of HD pathogenesis.http://dx.doi.org/10.1155/2019/3540974 |
| spellingShingle | Hyun Jung Park Sung Won Lee Wooseok Im Manho Kim Luc Van Kaer Seokmann Hong iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice Mediators of Inflammation |
| title | iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice |
| title_full | iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice |
| title_fullStr | iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice |
| title_full_unstemmed | iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice |
| title_short | iNKT Cell Activation Exacerbates the Development of Huntington’s Disease in R6/2 Transgenic Mice |
| title_sort | inkt cell activation exacerbates the development of huntington s disease in r6 2 transgenic mice |
| url | http://dx.doi.org/10.1155/2019/3540974 |
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