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| Home > Institute Collections > BN DZNE > BN DZNE-LIS > Nanobodies dismantle post‐pyroptotic ASC specks and counteract inflammation in vivo > print |
| Home > Institute Collections > BN DZNE > BN DZNE-LIS > Nanobodies dismantle post‐pyroptotic ASC specks and counteract inflammation in vivo > print |
| 001 | 284081 | ||
| 005 | 20260126111123.0 | ||
| 024 | 7 | _ | |a 10.15252/emmm.202115415 |2 doi |
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| 037 | _ | _ | |a DZNE-2026-00089 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Bertheloot, Damien |0 0000-0002-9495-706X |b 0 |
| 245 | _ | _ | |a Nanobodies dismantle post‐pyroptotic ASC specks and counteract inflammation in vivo |
| 260 | _ | _ | |a [London] |c 2022 |b Nature Publishing Group UK |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1769418357_1864 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
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| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 899 - ohne Topic (POF4-899) |0 G:(DE-HGF)POF4-899 |c POF4-899 |f POF IV |x 0 |
| 588 | _ | _ | |a Dataset connected to CrossRef, Journals: pub.dzne.de |
| 650 | _ | 7 | |a arthritis |2 Other |
| 650 | _ | 7 | |a extracellular inflammasomes |2 Other |
| 650 | _ | 7 | |a gout |2 Other |
| 650 | _ | 7 | |a nanobodies |2 Other |
| 650 | _ | 7 | |a pyroptosis |2 Other |
| 650 | _ | 7 | |a CARD Signaling Adaptor Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Inflammasomes |2 NLM Chemicals |
| 650 | _ | 7 | |a NLR Family, Pyrin Domain-Containing 3 Protein |2 NLM Chemicals |
| 650 | _ | 7 | |a Single-Domain Antibodies |2 NLM Chemicals |
| 650 | _ | 7 | |a Caspase 1 |0 EC 3.4.22.36 |2 NLM Chemicals |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a CARD Signaling Adaptor Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Caspase 1: metabolism |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Inflammasomes: metabolism |2 MeSH |
| 650 | _ | 2 | |a Inflammation: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a NLR Family, Pyrin Domain-Containing 3 Protein: metabolism |2 MeSH |
| 650 | _ | 2 | |a Pyroptosis |2 MeSH |
| 650 | _ | 2 | |a Single-Domain Antibodies |2 MeSH |
| 700 | 1 | _ | |a Wanderley, Carlos WS |b 1 |
| 700 | 1 | _ | |a Schneider, Ayda H |b 2 |
| 700 | 1 | _ | |a Schiffelers, Lisa DJ |0 0000-0003-2301-1610 |b 3 |
| 700 | 1 | _ | |a Wuerth, Jennifer D |0 0000-0002-3391-9633 |b 4 |
| 700 | 1 | _ | |a Tödtmann, Jan MP |0 0000-0002-9104-5858 |b 5 |
| 700 | 1 | _ | |a Maasewerd, Salie |0 0000-0002-4615-7252 |b 6 |
| 700 | 1 | _ | |a Hawwari, Ibrahim |b 7 |
| 700 | 1 | _ | |a Duthie, Fraser |b 8 |
| 700 | 1 | _ | |a Rohland, Cornelia |b 9 |
| 700 | 1 | _ | |a Secchim Ribeiro, Lucas |0 P:(DE-2719)9001782 |b 10 |u dzne |
| 700 | 1 | _ | |a Jenster, Lea-Marie |0 0000-0001-8580-4590 |b 11 |
| 700 | 1 | _ | |a Rosero, Nathalia |b 12 |
| 700 | 1 | _ | |a Tesfamariam, Yonas M |0 0000-0003-0106-7277 |b 13 |
| 700 | 1 | _ | |a Cunha, Fernando Q |b 14 |
| 700 | 1 | _ | |a Schmidt, Florian I |0 0000-0002-9979-9769 |b 15 |
| 700 | 1 | _ | |a Franklin, Bernardo S |b 16 |
| 773 | _ | _ | |a 10.15252/emmm.202115415 |g Vol. 14, no. 6, p. e15415 |0 PERI:(DE-600)2485479-7 |n 6 |p e15415 |t EMBO molecular medicine |v 14 |y 2022 |x 1757-4676 |
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| 856 | 4 | _ | |y OpenAccess |x pdfa |u https://pub.dzne.de/record/284081/files/EMBO%20Mol%20Med%20-%202022%20-%20Bertheloot%20-%20Nanobodies%20dismantle%20post%E2%80%90pyroptotic%20ASC%20specks%20and%20counteract%20inflammation%20in%20vivo.pdf?subformat=pdfa |
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