| |  Online-Ressource |
|---|
| Verfasst von: | Schultheiß, Christoph [VerfasserIn]  |
|---|
| | Paschold, Lisa [VerfasserIn] |
|---|
| | Mohebiany, Alma Nazlie [VerfasserIn] |
|---|
| | Escher, Moritz [VerfasserIn] |
|---|
| | Kattimani, Yogita Mallu [VerfasserIn] |
|---|
| | Müller, Melanie [VerfasserIn] |
|---|
| | Schmidt-Barbo, Paul [VerfasserIn] |
|---|
| | Willschel, Edith [VerfasserIn] |
|---|
| | Jonas, Hanna [VerfasserIn] |
|---|
| | Chinchuluun, Namuun [VerfasserIn] |
|---|
| | Hoffmann, Katrin [VerfasserIn] |
|---|
| | Czernilofsky, Felix [VerfasserIn] |
|---|
| | Dietrich, Sascha [VerfasserIn] |
|---|
| Titel: | A20 haploinsufficiency disturbs immune homeostasis and drives the transformation of lymphocytes with permissive antigen receptors |
|---|
| Verf.angabe: | Christoph Schultheiß, Lisa Paschold, Alma Nazlie Mohebiany, Moritz Escher, Yogita Mallu Kattimani, Melanie Müller, Paul Schmidt-Barbo, Edith Willschel, Hanna Jonas, Namuun Chinchuluun, Katrin Hoffmann, Felix Czernilofsky, Sascha Dietrich ... [und weitere] |
|---|
| E-Jahr: | 2024 |
|---|
| Jahr: | August 2024 |
|---|
| Umfang: | 16 S. |
|---|
| Illustrationen: | Diagramme, Illustrationen |
|---|
| Fussnoten: | Gesehen am 12.11.2024 |
|---|
| Titel Quelle: | Enthalten in: Science advances |
|---|
| Ort Quelle: | Washington, DC [u.a.] : Assoc., 2015 |
|---|
| Jahr Quelle: | 2024 |
|---|
| Band/Heft Quelle: | 10(2024), 34, Artikel-ID eadl3975, Seite 1-16 |
|---|
| ISSN Quelle: | 2375-2548 |
|---|
| Abstract: | Genetic TNFAIP3 (A20) inactivation is a classical somatic lymphoma lesion and the genomic trait in haploinsufficiency of A20 (HA20). In a cohort of 34 patients with HA20, we show that heterozygous TNFAIP3 loss skews immune repertoires toward lymphocytes with classical self-reactive antigen receptors typically found in B and T cell lymphomas. This skewing was mediated by a feed-forward tumor necrosis factor (TNF)/A20/nuclear factor κB (NF-κB) loop that shaped pre-lymphoma transcriptome signatures in clonally expanded B (CD81, BACH2, and NEAT1) or T (GATA3, TOX, and PDCD1) cells. The skewing was reversed by anti-TNF treatment but could also progress to overt lymphoma. Analysis of conditional TNFAIP3 knock-out mice reproduced the wiring of the TNF/A20/NF-κB signaling axis with permissive antigen receptors and suggested a distinct regulation in B and T cells. Together, patients with the genetic disorder HA20 provide an exceptional window into A20/TNF/NF-κB-mediated control of immune homeostasis and early steps of lymphomagenesis that remain clinically unrecognized. |
|---|
| DOI: | doi:10.1126/sciadv.adl3975 |
|---|
| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Resolving-System: https://doi.org/10.25673/116884 |
|---|
| | kostenfrei: Volltext: https://www.science.org/doi/10.1126/sciadv.adl3975 |
|---|
| | DOI: https://doi.org/10.1126/sciadv.adl3975 |
|---|
| | DOI: https://doi.org/10.25673/116884 |
|---|
| Datenträger: | Online-Ressource |
|---|
| Sprache: | eng |
|---|
| K10plus-PPN: | 1902715330 |
|---|
| Verknüpfungen: | → Zeitschrift |
|---|
A20 haploinsufficiency disturbs immune homeostasis and drives the transformation of lymphocytes with permissive antigen receptors / Schultheiß, Christoph [VerfasserIn]; August 2024 (Online-Ressource)
