@article{McFlederMakhotkinaGrohetal.2023,
  author    = {McFleder, Rhonda L. and Makhotkina, Anastasiia and Groh, Janos and Keber, Ursula and Imdahl, Fabian and Pe{\~n}a Mosca, Josefina and Peteranderl, Alina and Wu, Jingjing and Tabuchi, Sawako and Hoffmann, Jan and Karl, Ann-Kathrin and Pagenstecher, Axel and Vogel, J{\"o}rg and Beilhack, Andreas and Koprich, James B. and Brotchie, Jonathan M. and Saliba, Antoine-Emmanuel and Volkmann, Jens and Ip, Chi Wang},
  title     = {Brain-to-gut trafficking of alpha-synuclein by CD11c\(^+\) cells in a mouse model of Parkinson's disease},
  series = {Nature Communications},
  volume    = {14},
  journal   = {Nature Communications},
  doi       = {10.1038/s41467-023-43224-z},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-357696},
  year      = {2023},
  abstract  = {Inflammation in the brain and gut is a critical component of several neurological diseases, such as Parkinson's disease (PD). One trigger of the immune system in PD is aggregation of the pre-synaptic protein, α-synuclein (αSyn). Understanding the mechanism of propagation of αSyn aggregates is essential to developing disease-modifying therapeutics. Using a brain-first mouse model of PD, we demonstrate αSyn trafficking from the brain to the ileum of male mice. Immunohistochemistry revealed that the ileal αSyn aggregations are contained within CD11c+ cells. Using single-cell RNA sequencing, we demonstrate that ileal CD11c\(^+\) cells are microglia-like and the same subtype of cells is activated in the brain and ileum of PD mice. Moreover, by utilizing mice expressing the photo-convertible protein, Dendra2, we show that CD11c\(^+\) cells traffic from the brain to the ileum. Together these data provide a mechanism of αSyn trafficking between the brain and gut.},
  language  = {en}
}
@article{BadrMcFlederWuetal.2022,
  author    = {Badr, Mohammad and McFleder, Rhonda L. and Wu, Jingjing and Knorr, Susanne and Koprich, James B. and H{\"u}nig, Thomas and Brotchie, Jonathan M. and Volkmann, Jens and Lutz, Manfred B. and Ip, Chi Wang},
  title     = {Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson's disease mice},
  series = {Journal of Neuroinflammation},
  volume    = {19},
  journal   = {Journal of Neuroinflammation},
  doi       = {10.1186/s12974-022-02685-7},
  url       = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300580},
  year      = {2022},
  abstract  = {Background Regulatory CD4\(^+\)CD25\(^+\)FoxP3\(^+\) T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson's disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment. Methods Using the AAV1/2-A53T-α-synuclein Parkinson's disease mouse model that overexpresses the pathogenic human A53T-α-synuclein (hαSyn) variant in dopaminergic neurons of the substantia nigra, we assessed the neuroprotective and disease-modifying efficacy of a single intraperitoneal dose of CD28SA given at an early disease stage. Results CD28SA led to Treg expansion 3 days after delivery in hαSyn Parkinson's disease mice. At this timepoint, an early pro-inflammation was observed in vehicle-treated hαSyn Parkinson's disease mice with elevated percentages of CD8\(^+\)CD69\(^+\) T cells in brain and increased levels of interleukin-2 (IL-2) in the cervical lymph nodes and spleen. These immune responses were suppressed in CD28SA-treated hαSyn Parkinson's disease mice. Early treatment with CD28SA attenuated dopaminergic neurodegeneration in the SN of hαSyn Parkinson's disease mice accompanied with reduced brain numbers of activated CD4\(^+\), CD8\(^+\) T cells and CD11b\(^+\) microglia observed at the late disease-stage 10 weeks after AAV injection. In contrast, a later treatment 4 weeks after AAV delivery failed to reduce dopaminergic neurodegeneration. Conclusions Our data indicate that immune modulation by Treg expansion at a timepoint of overt inflammation is effective for treatment of hαSyn Parkinson's disease mice and suggest that the concept of early immune therapy could pose a disease-modifying option for Parkinson's disease patients.},
  language  = {en}
}