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@ARTICLE{Zhringer:300225,
      author       = {A. Zähringer and I. Morgado and D. Erny and F. Ingelfinger
                      and J. Gawron and S. Chatterjee and V. Wenger and D. Schmidt
                      and L. F. Schwöbel and R. C. Adams and M. Langenbach and A.
                      Hartmann and N. Osswald and J. Wolf and G. Schlunck and P.
                      S. Briquez and K. Grüter$^*$ and D. A. Ruess$^*$ and I.
                      Frew and A.-C. Burk$^*$ and V. Holzmüller and B. Grimbacher
                      and D. Michonneau and G. Andrieux and G. Socié and J.
                      Kolter and M. Börries$^*$ and M. Follo and F. Blaeschke$^*$
                      and L. Sevenich and M. Prinz and R. Zeiser and J. M.
                      Vinnakota},
      title        = {{A}h{R} activation mitigates graft-versus-host disease of
                      the central nervous system by reducing microglial {NF}-κ{B}
                      signaling.},
      journal      = {Blood advances},
      volume       = {9},
      number       = {12},
      issn         = {2473-9529},
      address      = {Washington, DC},
      publisher    = {American Society of Hematology},
      reportid     = {DKFZ-2025-00687},
      pages        = {2935-2952},
      year         = {2025},
      note         = {2025 Jun 24;9(12):2935-2952},
      abstract     = {Acute Graft-versus-Host Disease (GVHD) that occurs after
                      allogeneic hematopoietic cell transplantation (allo-HCT) can
                      affect the central nervous system (CNS). The majority of
                      allo-HCT patients receive antibiotic treatment, which alters
                      the microbiome and essential microbiome-derived metabolites.
                      We investigated the impact of microbiome modifications on
                      CNS-GVHD and therapeutic strategies to overcome the
                      microbiome-derived metabolite depletion. Antibiotic
                      treatment of mice undergoing allo-HCT increased microglia
                      numbers in the brain, indicating increased inflammation. In
                      addition, microglia morphology shifted towards a highly
                      branched phenotype. Consistent with a pro-inflammatory
                      phenotype microglia exhibited increased NF-κB and Src
                      activity. Antibiotic treatment caused the depletion of the
                      bacteria-derived arylhydrocarbon receptor (AhR) ligand
                      indole-3-acetate in the brain. Conversely, treatment of
                      primary microglia with the AhR-ligand- 6-formylindolo (3,
                      2-b) carbazole (FICZ) reduced NF-κB activity and phagocytic
                      potential. Microglia expansion and morphological changes
                      were reversed by AhR-ligand-FICZ-treatment. Moreover, the
                      AhR-ligand indole-3-acetate was also reduced in the CNS of
                      patients that developed acute GVHD concomitant with
                      increased microglial NF-κB expression. In summary, we
                      demonstrated that antibiotic treatment and a subsequent
                      decrease of AhR-ligands resulted in increased microglia
                      activation during CNS-GVHD. FICZ-treatment hampered CNS
                      inflammation by inhibiting NF-κB activity, thereby
                      providing a metabolic modifier to interfere with pathogenic
                      microglia signaling and CNS-GVHD in vivo.},
      cin          = {D270 / FR01},
      ddc          = {610},
      cid          = {I:(DE-He78)D270-20160331 / I:(DE-He78)FR01-20160331},
      pnm          = {314 - Immunologie und Krebs (POF4-314)},
      pid          = {G:(DE-HGF)POF4-314},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40163754},
      doi          = {10.1182/bloodadvances.2024015000},
      url          = {https://inrepo02.dkfz.de/record/300225},
}