% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Fiedler:275758,
      author       = {T. Fiedler$^*$ and R. Fairless$^*$ and K. Pichi$^*$ and R.
                      Fischer and F. Richter and R. E. Kontermann and K.
                      Pfizenmaier and R. Diem$^*$ and S. Williams$^*$},
      title        = {{C}o-modulation of {TNFR}1 and {TNFR}2 in an animal model
                      of multiple sclerosis.},
      journal      = {Journal of neuroinflammation},
      volume       = {20},
      number       = {1},
      issn         = {1742-2094},
      address      = {London},
      publisher    = {BioMed Central},
      reportid     = {DKFZ-2023-00857},
      pages        = {100},
      year         = {2023},
      note         = {#EA:B320#LA:B320#},
      abstract     = {Tumour necrosis factor (TNF) is a pleiotropic cytokine and
                      master regulator of the immune system. It acts through two
                      receptors resulting in often opposing biological effects,
                      which may explain the lack of therapeutic potential obtained
                      so far in multiple sclerosis (MS) with non-receptor-specific
                      anti-TNF therapeutics. Under neuroinflammatory conditions,
                      such as MS, TNF receptor-1 (TNFR1) is believed to mediate
                      the pro-inflammatory activities associated with TNF, whereas
                      TNF receptor-2 (TNFR2) may instead induce anti-inflammatory
                      effects as well as promote remyelination and
                      neuroprotection. In this study, we have investigated the
                      therapeutic potential of blocking TNFR1 whilst
                      simultaneously stimulating TNFR2 in a mouse model of
                      MS.Experimental autoimmune encephalomyelitis (EAE) was
                      induced with myelin oligodendrocyte glycoprotein (MOG35-55)
                      in humanized TNFR1 knock-in mice. These were treated with a
                      human-specific TNFR1-selective antagonistic antibody (H398)
                      and a mouse-specific TNFR2 agonist (EHD2-sc-mTNFR2), both in
                      combination and individually. Histopathological analysis of
                      spinal cords was performed to investigate demyelination and
                      inflammatory infiltration, as well as axonal and neuronal
                      degeneration. Retinas were examined for any protective
                      effects on retinal ganglion cell (RGC) degeneration and
                      neuroprotective signalling pathways analysed by Western
                      blotting.TNFR modulation successfully ameliorated symptoms
                      of EAE and reduced demyelination, inflammatory infiltration
                      and axonal degeneration. Furthermore, the combinatorial
                      approach of blocking TNFR1 and stimulating TNFR2 signalling
                      increased RGC survival and promoted the phosphorylation of
                      Akt and NF-κB, both known to mediate neuroprotection.These
                      results further support the potential of regulating the
                      balance of TNFR signalling, through the co-modulation of
                      TNFR1 and TNFR2 activity, as a novel therapeutic approach in
                      treating inflammatory demyelinating disease.},
      keywords     = {EAE (Other) / Neuroinflammation (Other) / Neuroprotection
                      (Other) / TNFR1 (Other) / TNFR2 (Other)},
      cin          = {B320 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)B320-20160331 / I:(DE-He78)HD01-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37122019},
      doi          = {10.1186/s12974-023-02784-z},
      url          = {https://inrepo02.dkfz.de/record/275758},
}