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1000 Titel
  • Modeling MyD88 Deficiency In Vitro Provides New Insights in Its Function
1000 Autor/in
  1. Craig-Müller, Nils |
  2. Hammad, Ruba |
  3. Elling, Roland |
  4. Alzubi, Jamal |
  5. Timm, Barbara |
  6. Kolter, Julia |
  7. Knelangen, Nele |
  8. Bednarski, Christien |
  9. Gläser, Birgitta |
  10. Ammann, Sandra |
  11. Ivics, Zoltan |
  12. Fischer, Judith |
  13. Speckmann, Carsten |
  14. Schwarz, Klaus |
  15. Lachmann, Nico |
  16. Ehl, Stephan |
  17. Moritz, Thomas |
  18. Henneke, Philipp |
  19. Cathomen, Toni |
1000 Erscheinungsjahr 2020
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-12-23
1000 Erschienen in
1000 Quellenangabe
  • 11:608802
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.3389/fimmu.2020.608802 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786022/ |
1000 Ergänzendes Material
  • https://www.frontiersin.org/articles/10.3389/fimmu.2020.608802/full#h11 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Inherited defects in MyD88 and IRAK4, two regulators in Toll-like receptor (TLR) signaling, are clinically highly relevant, but still incompletely understood. MyD88- and IRAK4-deficient patients are exceedingly susceptible to a narrow spectrum of pathogens, with ∼50% lethality in the first years of life. To better understand the underlying molecular and cellular characteristics that determine disease progression, we aimed at modeling the cellular response to pathogens in vitro. To this end, we determined the immunophenotype of monocytes and macrophages derived from MyD88- and IRAK4-deficient patients. We recognized that macrophages derived from both patients were particularly poorly activated by streptococci, indicating that both signaling intermediates are essential for the immune response to facultative pathogens. To characterize this defect in more detail, we generated induced pluripotent stem cells (iPSCs) of fibroblasts derived from an MyD88-deficient patient. The underlying genetic defect was corrected using Sleeping Beauty transposon vectors encoding either the long (L) or the short (S) MYD88 isoform, respectively. Macrophages derived from these iPSC lines (iMacs) expressed typical macrophage markers, stably produced either MyD88 isoform, and showed robust phagocytic activity. Notably, iMacs expressing MyD88-L, but not MyD88-S, exhibited similar responses to external stimuli, including cytokine release patterns, as compared to genetically normal iMacs. Thus, the two MyD88 isoforms assume distinct functions in signaling. In conclusion, iPSC technology, in combination with efficient myeloid differentiation protocols, provides a valuable and inexhaustible source of macrophages, which can be used for disease modeling. Moreover, iPSC-derived macrophages may eventually aid in stabilizing MyD88-deficient patients during pyogenic infections.
1000 Sacherschließung
lokal IRAK4
lokal MyD88
lokal Toll-like receptor
lokal cell therapy
lokal iMac
lokal induced pluripotent stem cells (iPSC)
lokal transposon
lokal gene therapy
gnd 1130259315 Induzierte pluripotente Stammzelle
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. https://d-nb.info/gnd/1219184039|https://d-nb.info/gnd/1225082188|https://orcid.org/0000-0002-2209-4154|https://orcid.org/0000-0003-4284-2006|https://d-nb.info/gnd/1225082358|https://orcid.org/0000-0002-3268-8124|https://d-nb.info/gnd/1225082463|https://orcid.org/0000-0002-4787-3293|https://orcid.org/0000-0002-5792-7910|https://orcid.org/0000-0003-0385-1890|https://orcid.org/0000-0002-7803-6658|https://orcid.org/0000-0002-8580-8118|https://orcid.org/0000-0002-6217-1556|https://orcid.org/0000-0001-5455-2394|https://orcid.org/0000-0002-4245-1497|https://orcid.org/0000-0002-9265-2721|https://frl.publisso.de/adhoc/uri/ICBNb3JpdHosIFRob21hcyAgICA=|https://orcid.org/0000-0001-7314-7984|https://orcid.org/0000-0002-7757-4630
1000 Label
1000 Förderer
  1. Bundesministerium für Bildung und Forschung |
  2. Else Kröner-Fresenius-Stiftung |
  3. Deutsche Forschungsgemeinschaft |
  4. Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg |
  5. Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg |
1000 Fördernummer
  1. iMacNet–01EK1602; 01GL1746A; IFB–01EO1303
  2. -
  3. HE3127/9; HE3127/12; SFB/TRR167
  4. 3096997002
  5. -
1000 Förderprogramm
  1. -
  2. -
  3. -
  4. -
  5. Open access funding
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Bildung und Forschung |
    1000 Förderprogramm -
    1000 Fördernummer iMacNet–01EK1602; 01GL1746A; IFB–01EO1303
  2. 1000 joinedFunding-child
    1000 Förderer Else Kröner-Fresenius-Stiftung |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft |
    1000 Förderprogramm -
    1000 Fördernummer HE3127/9; HE3127/12; SFB/TRR167
  4. 1000 joinedFunding-child
    1000 Förderer Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg |
    1000 Förderprogramm -
    1000 Fördernummer 3096997002
  5. 1000 joinedFunding-child
    1000 Förderer Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg |
    1000 Förderprogramm Open access funding
    1000 Fördernummer -
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6432425.rdf
1000 Erstellt am 2022-03-22T13:37:17.533+0100
1000 Erstellt von 323
1000 beschreibt frl:6432425
1000 Bearbeitet von 317
1000 Zuletzt bearbeitet Wed Apr 20 12:21:44 CEST 2022
1000 Objekt bearb. Wed Apr 20 12:21:08 CEST 2022
1000 Vgl. frl:6432425
1000 Oai Id
  1. oai:frl.publisso.de:frl:6432425 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
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