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CAR/FoxP3-engineere...
CAR/FoxP3-engineered T regulatory cells target the CNS and suppress EAE upon intranasal delivery
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- Fransson, Moa (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Piras, Elena (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Burman, Joachim (författare)
- Uppsala universitet,Neurologi
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- Nilsson, Berith (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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- Essand, Magnus (författare)
- Uppsala universitet,Klinisk immunologi,Science for Life Laboratory, SciLifeLab
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Lu, Binfeng (författare)
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- Harris, Robert A (författare)
- Karolinska Institutet
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- Magnusson, Peetra U (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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- Brittebo, Eva (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Loskog, Angelica Si (författare)
- Uppsala universitet,Science for Life Laboratory, SciLifeLab,Klinisk immunologi
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(creator_code:org_t)
- 2012-05-30
- 2012
- Engelska.
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Ingår i: Journal of Neuroinflammation. - : Springer Science and Business Media LLC. - 1742-2094. ; 9, s. 112-
- Relaterad länk:
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https://uu.diva-port... (primary) (Raw object)
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https://jneuroinflam...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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Abstract
Ämnesord
Stäng
- BACKGROUND:Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS). In the murine experimental autoimmune encephalomyelitis (EAE) model of MS, T regulatory (Treg) cell therapy has proved to be beneficial, but generation of stable CNS-targeting Tregs needs further development. Here, we propose gene engineering to achieve CNS-targeting Tregs from naive CD4 cells and demonstrate their efficacy in the EAE model.METHODSCD4+T cells were modified utilizing a lentiviral vector system to express a chimeric antigen receptor (CAR) targeting myelin oligodendrocyte glycoprotein (MOG) in trans with the murine FoxP3 gene that drives Treg differentiation. The cells were evaluated in vitro for suppressive capacity and in C57BL/6 mice to treat EAE. Cells were administered by intranasal (i.n.) cell delivery.RESULTSThe engineered Tregs demonstrated suppressive capacity in vitro and could efficiently access various regions in the brain via i.n cell delivery. Clinical score 3 EAE mice were treated and the engineered Tregs suppressed ongoing encephalomyelitis as demonstrated by reduced disease symptoms as well as decreased IL-12 and IFNgamma mRNAs in brain tissue. Immunohistochemical markers for myelination (MBP) and reactive astrogliosis (GFAP) confirmed recovery in mice treated with engineered Tregs compared to controls. Symptomfree mice were echallenged with a second EAE-inducing inoculum but remained healthy, demonstrating the sustained effect of engineered Tregs.CONCLUSIONCNS-targeting Tregs delivered i.n. localized to the CNS and efficiently suppressed ongoing inflammation leading to diminished disease symptoms.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Neurologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Neurology (hsv//eng)
Nyckelord
- MS
- redirected cells
- T regulatory cells
- EAE
- FoxP3
- myelin oligodendrocyte glycoprotein
- Neurology
- Neurologi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Fransson, Moa
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Piras, Elena
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Burman, Joachim
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Nilsson, Berith
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Essand, Magnus
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Lu, Binfeng
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visa fler...
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Harris, Robert A
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Magnusson, Peetr ...
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Brittebo, Eva
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Loskog, Angelica ...
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visa färre...
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Neurologi
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Journal of Neuro ...
- Av lärosätet
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Uppsala universitet
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Karolinska Institutet