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@ARTICLE{Bertheloot:284081,
      author       = {Bertheloot, Damien and Wanderley, Carlos WS and Schneider,
                      Ayda H and Schiffelers, Lisa DJ and Wuerth, Jennifer D and
                      Tödtmann, Jan MP and Maasewerd, Salie and Hawwari, Ibrahim
                      and Duthie, Fraser and Rohland, Cornelia and Secchim
                      Ribeiro, Lucas and Jenster, Lea-Marie and Rosero, Nathalia
                      and Tesfamariam, Yonas M and Cunha, Fernando Q and Schmidt,
                      Florian I and Franklin, Bernardo S},
      title        = {{N}anobodies dismantle post‐pyroptotic {ASC} specks and
                      counteract inflammation in vivo},
      journal      = {EMBO molecular medicine},
      volume       = {14},
      number       = {6},
      issn         = {1757-4676},
      address      = {[London]},
      publisher    = {Nature Publishing Group UK},
      reportid     = {DZNE-2026-00089},
      pages        = {e15415},
      year         = {2022},
      abstract     = {Inflammasomes sense intracellular clues of infection,
                      damage, or metabolic imbalances. Activated inflammasome
                      sensors polymerize the adaptor ASC into micron-sized
                      'specks' to maximize caspase-1 activation and the maturation
                      of IL-1 cytokines. Caspase-1 also drives pyroptosis, a lytic
                      cell death characterized by leakage of intracellular content
                      to the extracellular space. ASC specks are released among
                      cytosolic content, and accumulate in tissues of patients
                      with chronic inflammation. However, if extracellular ASC
                      specks contribute to disease, or are merely inert remnants
                      of cell death remains unknown. Here, we show that
                      camelid-derived nanobodies against ASC (VHHASC ) target and
                      disassemble post-pyroptotic inflammasomes, neutralizing
                      their prionoid, and inflammatory functions. Notably,
                      pyroptosis-driven membrane perforation and exposure of ASC
                      specks to the extracellular environment allowed VHHASC to
                      target inflammasomes while preserving pre-pyroptotic IL-1β
                      release, essential to host defense. Systemically
                      administrated mouse-specific VHHASC attenuated inflammation
                      and clinical gout, and antigen-induced arthritis disease.
                      Hence, VHHASC neutralized post-pyroptotic inflammasomes
                      revealing a previously unappreciated role for these
                      complexes in disease. VHHASC are the first biologicals that
                      disassemble pre-formed inflammasomes while preserving their
                      functions in host defense.},
      keywords     = {Animals / CARD Signaling Adaptor Proteins: metabolism /
                      Caspase 1: metabolism / Humans / Inflammasomes: metabolism /
                      Inflammation: metabolism / Mice / NLR Family, Pyrin
                      Domain-Containing 3 Protein: metabolism / Pyroptosis /
                      Single-Domain Antibodies / arthritis (Other) / extracellular
                      inflammasomes (Other) / gout (Other) / nanobodies (Other) /
                      pyroptosis (Other) / CARD Signaling Adaptor Proteins (NLM
                      Chemicals) / Inflammasomes (NLM Chemicals) / NLR Family,
                      Pyrin Domain-Containing 3 Protein (NLM Chemicals) /
                      Single-Domain Antibodies (NLM Chemicals) / Caspase 1 (NLM
                      Chemicals)},
      ddc          = {610},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      doi          = {10.15252/emmm.202115415},
      url          = {https://pub.dzne.de/record/284081},
}