Cover Image

Perinatal dysfunction of innate immunity in cystic fibrosis: cystic fibrosis

In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate imm...

Full description

Saved in:
Bibliographic Details
Main Authors: Jaudas, Florian (Author) , Bartenschlager, Florian (Author) , Shashikadze, Bachuki (Author) , Santamaria, Gianluca (Author) , Reichart, Daniel (Author) , Schnell, Alexander (Author) , Stöckl, Jan Bernd (Author) , Degroote, Roxane L. (Author) , Cambra, Josep M. (Author) , Graeber, Simon Y. (Author) , Bähr, Andrea (Author) , Kartmann, Heike (Author) , Stefanska, Monika (Author) , Liu, Huan (Author) , Naumann-Bartsch, Nora (Author) , Bruns, Heiko (Author) , Berges, Johannes (Author) , Hanselmann, Lea (Author) , Stirm, Michael (Author) , Krebs, Stefan (Author) , Deeg, Cornelia A. (Author) , Blum, Helmut (Author) , Schulz, Christian (Author) , Zawada, Dorota (Author) , Janda, Melanie (Author) , Caballero-Posadas, Ignacio (Author) , Kunzelmann, Karl (Author) , Moretti, Alessandra (Author) , Laugwitz, Karl-Ludwig (Author) , Kupatt, Christian (Author) , Saalmüller, Armin (Author) , Fröhlich, Thomas (Author) , Wolf, Eckhard (Author) , Mall, Marcus A. (Author) , Mundhenk, Lars (Author) , Gerner, Wilhelm (Author) , Klymiuk, Nikolai (Author)
Format: Article (Journal)
Language:English
Published: 22 January 2025
In: Science translational medicine
Year: 2025, Volume: 17, Issue: 782, Pages: 1-17
ISSN:1946-6242
DOI:10.1126/scitranslmed.adk9145
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1126/scitranslmed.adk9145
Verlag, lizenzpflichtig, Volltext: http://www.science.org/doi/10.1126/scitranslmed.adk9145
Get full text
Author Notes:Florian Jaudas, Florian Bartenschlager, Bachuki Shashikadze, Gianluca Santamaria, Daniel Reichart, Alexander Schnell, Jan Bernd Stöckl, Roxane L. Degroote, Josep M. Cambra, Simon Y. Graeber, Andrea Bähr, Heike Kartmann, Monika Stefanska, Huan Liu, Nora Naumann-Bartsch, Heiko Bruns, Johannes Berges, Lea Hanselmann, Michael Stirm, Stefan Krebs, Cornelia A. Deeg, Helmut Blum, Christian Schulz, Dorota Zawada, Melanie Janda, Ignacio Caballero-Posadas, Karl Kunzelmann, Alessandra Moretti, Karl-Ludwig Laugwitz, Christian Kupatt, Armin Saalmüller, Thomas Fröhlich, Eckhard Wolf, Marcus A. Mall, Lars Mundhenk, Wilhelm Gerner, Nikolai Klymiuk

MARC

LEADER 00000naa a2200000 c 4500
001 1932164057
003 DE-627
005 20250731102352.0
007 cr uuu---uuuuu
008 250731s2025 xx |||||o 00| ||eng c
024 7 |a 10.1126/scitranslmed.adk9145  |2 doi 
035 |a (DE-627)1932164057 
035 |a (DE-599)KXP1932164057 
040 |a DE-627  |b ger  |c DE-627  |e rda 
041 |a eng 
084 |a 33  |2 sdnb 
100 1 |a Jaudas, Florian  |e VerfasserIn  |0 (DE-588)1226116523  |0 (DE-627)174637764X  |4 aut 
245 1 0 |a Perinatal dysfunction of innate immunity in cystic fibrosis  |b cystic fibrosis  |c Florian Jaudas, Florian Bartenschlager, Bachuki Shashikadze, Gianluca Santamaria, Daniel Reichart, Alexander Schnell, Jan Bernd Stöckl, Roxane L. Degroote, Josep M. Cambra, Simon Y. Graeber, Andrea Bähr, Heike Kartmann, Monika Stefanska, Huan Liu, Nora Naumann-Bartsch, Heiko Bruns, Johannes Berges, Lea Hanselmann, Michael Stirm, Stefan Krebs, Cornelia A. Deeg, Helmut Blum, Christian Schulz, Dorota Zawada, Melanie Janda, Ignacio Caballero-Posadas, Karl Kunzelmann, Alessandra Moretti, Karl-Ludwig Laugwitz, Christian Kupatt, Armin Saalmüller, Thomas Fröhlich, Eckhard Wolf, Marcus A. Mall, Lars Mundhenk, Wilhelm Gerner, Nikolai Klymiuk 
264 1 |c 22 January 2025 
300 |b Illustrationen, Diagramme 
300 |a 17 
336 |a Text  |b txt  |2 rdacontent 
337 |a Computermedien  |b c  |2 rdamedia 
338 |a Online-Ressource  |b cr  |2 rdacarrier 
500 |a Gesehen am 31.07.2025 
520 |a In patients with cystic fibrosis (CF), repeated cycles of infection and inflammation eventually lead to fatal lung damage. Although diminished mucus clearance can be restored by highly effective CFTR modulator therapy, inflammation and infection often persist. To elucidate the role of the innate immune system in CF etiology, we investigated a CF pig model and compared these results with those for preschool children with CF. In newborn CF pigs, we observed changes in lung immune cell composition before the onset of infection that were dominated by increased monocyte infiltration, whereas neutrophil numbers remained constant. Flow cytometric and transcriptomic profiling revealed that the infiltrating myeloid cells displayed a more immature status. Cells with comparably immature transcriptomic profiles were enriched in the blood of CF pigs at birth as well as in preschool children with CF. This pattern coincided with decreased CD16 expression in the myeloid cells of both pigs and humans, which translated into lower phagocytic activity and reduced production of reactive oxygen species in both species. These results were indicative of a congenital, translationally conserved, and functionally relevant aberration of the immune system in CF. In newborn wild-type pigs, CFTR transcription in immune cells, including lung-derived and circulating monocytes, isolated from the bone marrow, thymus, spleen, and blood was below the detection limits of highly sensitive assays, suggesting an indirect etiology of the observed effects. Our findings highlight the need for additional immunological treatments to target innate immune deficits in patients with CF. 
700 1 |a Bartenschlager, Florian  |e VerfasserIn  |4 aut 
700 1 |a Shashikadze, Bachuki  |e VerfasserIn  |4 aut 
700 1 |a Santamaria, Gianluca  |e VerfasserIn  |4 aut 
700 1 |a Reichart, Daniel  |e VerfasserIn  |4 aut 
700 1 |a Schnell, Alexander  |e VerfasserIn  |4 aut 
700 1 |a Stöckl, Jan Bernd  |e VerfasserIn  |4 aut 
700 1 |a Degroote, Roxane L.  |e VerfasserIn  |4 aut 
700 1 |a Cambra, Josep M.  |e VerfasserIn  |4 aut 
700 1 |a Graeber, Simon Y.  |e VerfasserIn  |4 aut 
700 1 |a Bähr, Andrea  |e VerfasserIn  |4 aut 
700 1 |a Kartmann, Heike  |e VerfasserIn  |4 aut 
700 1 |a Stefanska, Monika  |e VerfasserIn  |4 aut 
700 1 |a Liu, Huan  |e VerfasserIn  |4 aut 
700 1 |a Naumann-Bartsch, Nora  |e VerfasserIn  |4 aut 
700 1 |a Bruns, Heiko  |e VerfasserIn  |4 aut 
700 1 |a Berges, Johannes  |e VerfasserIn  |4 aut 
700 1 |a Hanselmann, Lea  |e VerfasserIn  |4 aut 
700 1 |a Stirm, Michael  |e VerfasserIn  |4 aut 
700 1 |a Krebs, Stefan  |e VerfasserIn  |4 aut 
700 1 |a Deeg, Cornelia A.  |e VerfasserIn  |4 aut 
700 1 |a Blum, Helmut  |e VerfasserIn  |4 aut 
700 1 |a Schulz, Christian  |d 1976-  |e VerfasserIn  |0 (DE-588)129423122  |0 (DE-627)396080618  |0 (DE-576)29765280X  |4 aut 
700 1 |a Zawada, Dorota  |e VerfasserIn  |4 aut 
700 1 |a Janda, Melanie  |e VerfasserIn  |4 aut 
700 1 |a Caballero-Posadas, Ignacio  |e VerfasserIn  |4 aut 
700 1 |a Kunzelmann, Karl  |e VerfasserIn  |4 aut 
700 1 |a Moretti, Alessandra  |e VerfasserIn  |4 aut 
700 1 |a Laugwitz, Karl-Ludwig  |e VerfasserIn  |4 aut 
700 1 |a Kupatt, Christian  |e VerfasserIn  |4 aut 
700 1 |a Saalmüller, Armin  |e VerfasserIn  |4 aut 
700 1 |a Fröhlich, Thomas  |e VerfasserIn  |4 aut 
700 1 |a Wolf, Eckhard  |e VerfasserIn  |4 aut 
700 1 |a Mall, Marcus A.  |e VerfasserIn  |4 aut 
700 1 |a Mundhenk, Lars  |e VerfasserIn  |4 aut 
700 1 |a Gerner, Wilhelm  |e VerfasserIn  |4 aut 
700 1 |a Klymiuk, Nikolai  |e VerfasserIn  |4 aut 
773 0 8 |i Enthalten in  |t Science translational medicine  |d Washington, DC : AAAS, 2009  |g 17(2025), 782 vom: Jan., Artikel-ID eadk9145, Seite 1-17  |h Online-Ressource  |w (DE-627)610606980  |w (DE-600)2518839-2  |w (DE-576)312705638  |x 1946-6242  |7 nnas  |a Perinatal dysfunction of innate immunity in cystic fibrosis cystic fibrosis 
773 1 8 |g volume:17  |g year:2025  |g number:782  |g month:01  |g elocationid:eadk9145  |g pages:1-17  |g extent:17  |a Perinatal dysfunction of innate immunity in cystic fibrosis cystic fibrosis 
856 4 0 |u https://doi.org/10.1126/scitranslmed.adk9145  |x Verlag  |x Resolving-System  |z lizenzpflichtig  |3 Volltext 
856 4 0 |u http://www.science.org/doi/10.1126/scitranslmed.adk9145  |x Verlag  |z lizenzpflichtig  |3 Volltext 
951 |a AR 
992 |a 20250731 
993 |a Article 
994 |a 2025 
998 |g 129423122  |a Schulz, Christian  |m 129423122:Schulz, Christian  |d 60000  |d 65400  |e 60000PS129423122  |e 65400PS129423122  |k 0/60000/  |k 1/60000/65400/  |p 23 
999 |a KXP-PPN1932164057  |e 4751096664 
BIB |a Y 
SER |a journal 
JSO |a {"title":[{"title":"Perinatal dysfunction of innate immunity in cystic fibrosis","subtitle":"cystic fibrosis","title_sort":"Perinatal dysfunction of innate immunity in cystic fibrosis"}],"person":[{"role":"aut","roleDisplay":"VerfasserIn","display":"Jaudas, Florian","given":"Florian","family":"Jaudas"},{"roleDisplay":"VerfasserIn","display":"Bartenschlager, Florian","role":"aut","family":"Bartenschlager","given":"Florian"},{"given":"Bachuki","family":"Shashikadze","role":"aut","roleDisplay":"VerfasserIn","display":"Shashikadze, Bachuki"},{"given":"Gianluca","family":"Santamaria","role":"aut","display":"Santamaria, Gianluca","roleDisplay":"VerfasserIn"},{"display":"Reichart, Daniel","roleDisplay":"VerfasserIn","role":"aut","family":"Reichart","given":"Daniel"},{"role":"aut","display":"Schnell, Alexander","roleDisplay":"VerfasserIn","given":"Alexander","family":"Schnell"},{"family":"Stöckl","given":"Jan Bernd","display":"Stöckl, Jan Bernd","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Roxane L.","family":"Degroote","role":"aut","roleDisplay":"VerfasserIn","display":"Degroote, Roxane L."},{"role":"aut","roleDisplay":"VerfasserIn","display":"Cambra, Josep M.","given":"Josep M.","family":"Cambra"},{"roleDisplay":"VerfasserIn","display":"Graeber, Simon Y.","role":"aut","family":"Graeber","given":"Simon Y."},{"given":"Andrea","family":"Bähr","role":"aut","roleDisplay":"VerfasserIn","display":"Bähr, Andrea"},{"family":"Kartmann","given":"Heike","display":"Kartmann, Heike","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Monika","family":"Stefanska","role":"aut","roleDisplay":"VerfasserIn","display":"Stefanska, Monika"},{"given":"Huan","family":"Liu","role":"aut","roleDisplay":"VerfasserIn","display":"Liu, Huan"},{"given":"Nora","family":"Naumann-Bartsch","role":"aut","roleDisplay":"VerfasserIn","display":"Naumann-Bartsch, Nora"},{"family":"Bruns","given":"Heiko","display":"Bruns, Heiko","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Johannes","family":"Berges","role":"aut","roleDisplay":"VerfasserIn","display":"Berges, Johannes"},{"family":"Hanselmann","given":"Lea","display":"Hanselmann, Lea","roleDisplay":"VerfasserIn","role":"aut"},{"given":"Michael","family":"Stirm","role":"aut","display":"Stirm, Michael","roleDisplay":"VerfasserIn"},{"role":"aut","roleDisplay":"VerfasserIn","display":"Krebs, Stefan","given":"Stefan","family":"Krebs"},{"display":"Deeg, Cornelia A.","roleDisplay":"VerfasserIn","role":"aut","family":"Deeg","given":"Cornelia A."},{"display":"Blum, Helmut","roleDisplay":"VerfasserIn","role":"aut","family":"Blum","given":"Helmut"},{"display":"Schulz, Christian","roleDisplay":"VerfasserIn","role":"aut","family":"Schulz","given":"Christian"},{"given":"Dorota","family":"Zawada","role":"aut","roleDisplay":"VerfasserIn","display":"Zawada, Dorota"},{"roleDisplay":"VerfasserIn","display":"Janda, Melanie","role":"aut","family":"Janda","given":"Melanie"},{"given":"Ignacio","family":"Caballero-Posadas","role":"aut","display":"Caballero-Posadas, Ignacio","roleDisplay":"VerfasserIn"},{"family":"Kunzelmann","given":"Karl","display":"Kunzelmann, Karl","roleDisplay":"VerfasserIn","role":"aut"},{"family":"Moretti","given":"Alessandra","display":"Moretti, Alessandra","roleDisplay":"VerfasserIn","role":"aut"},{"display":"Laugwitz, Karl-Ludwig","roleDisplay":"VerfasserIn","role":"aut","family":"Laugwitz","given":"Karl-Ludwig"},{"given":"Christian","family":"Kupatt","role":"aut","roleDisplay":"VerfasserIn","display":"Kupatt, Christian"},{"given":"Armin","family":"Saalmüller","role":"aut","roleDisplay":"VerfasserIn","display":"Saalmüller, Armin"},{"family":"Fröhlich","given":"Thomas","roleDisplay":"VerfasserIn","display":"Fröhlich, Thomas","role":"aut"},{"display":"Wolf, Eckhard","roleDisplay":"VerfasserIn","role":"aut","family":"Wolf","given":"Eckhard"},{"given":"Marcus A.","family":"Mall","role":"aut","roleDisplay":"VerfasserIn","display":"Mall, Marcus A."},{"family":"Mundhenk","given":"Lars","roleDisplay":"VerfasserIn","display":"Mundhenk, Lars","role":"aut"},{"role":"aut","display":"Gerner, Wilhelm","roleDisplay":"VerfasserIn","given":"Wilhelm","family":"Gerner"},{"display":"Klymiuk, Nikolai","roleDisplay":"VerfasserIn","role":"aut","family":"Klymiuk","given":"Nikolai"}],"type":{"media":"Online-Ressource","bibl":"article-journal"},"note":["Gesehen am 31.07.2025"],"recId":"1932164057","language":["eng"],"origin":[{"dateIssuedDisp":"22 January 2025","dateIssuedKey":"2025"}],"id":{"eki":["1932164057"],"doi":["10.1126/scitranslmed.adk9145"]},"name":{"displayForm":["Florian Jaudas, Florian Bartenschlager, Bachuki Shashikadze, Gianluca Santamaria, Daniel Reichart, Alexander Schnell, Jan Bernd Stöckl, Roxane L. Degroote, Josep M. Cambra, Simon Y. Graeber, Andrea Bähr, Heike Kartmann, Monika Stefanska, Huan Liu, Nora Naumann-Bartsch, Heiko Bruns, Johannes Berges, Lea Hanselmann, Michael Stirm, Stefan Krebs, Cornelia A. Deeg, Helmut Blum, Christian Schulz, Dorota Zawada, Melanie Janda, Ignacio Caballero-Posadas, Karl Kunzelmann, Alessandra Moretti, Karl-Ludwig Laugwitz, Christian Kupatt, Armin Saalmüller, Thomas Fröhlich, Eckhard Wolf, Marcus A. Mall, Lars Mundhenk, Wilhelm Gerner, Nikolai Klymiuk"]},"physDesc":[{"extent":"17 S.","noteIll":"Illustrationen, Diagramme"}],"relHost":[{"pubHistory":["1.2009 -"],"part":{"extent":"17","volume":"17","text":"17(2025), 782 vom: Jan., Artikel-ID eadk9145, Seite 1-17","pages":"1-17","issue":"782","year":"2025"},"disp":"Perinatal dysfunction of innate immunity in cystic fibrosis cystic fibrosisScience translational medicine","type":{"bibl":"periodical","media":"Online-Ressource"},"note":["Gesehen am 13.09.2021"],"language":["eng"],"corporate":[{"roleDisplay":"Herausgebendes Organ","display":"American Association for the Advancement of Science","role":"isb"}],"recId":"610606980","title":[{"title_sort":"Science translational medicine","title":"Science translational medicine","subtitle":"integrating medicine and science"}],"physDesc":[{"extent":"Online-Ressource"}],"origin":[{"dateIssuedKey":"2009","publisher":"AAAS","dateIssuedDisp":"2009-","publisherPlace":"Washington, DC"}],"id":{"issn":["1946-6242"],"eki":["610606980"],"zdb":["2518839-2"]},"name":{"displayForm":["American Association for the Advancement of Science"]}}]} 
SRT |a JAUDASFLORPERINATALD2220 

Similar Items