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RNase T2 restricts TLR13-mediated autoinflammation in vivo

RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role in processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition to its positive regulatory role, RNase T2 also restricts RNA recog...

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Hauptverfasser: Gómez Díaz, Carlos (VerfasserIn) , Greulich, Wilhelm (VerfasserIn) , Wefers, Benedikt (VerfasserIn) , Wang, Meiyue (VerfasserIn) , Bolsega, Silvia (VerfasserIn) , Effern, Maike (VerfasserIn) , Varga, Daniel P. (VerfasserIn) , Han, Zhe (VerfasserIn) , Chen, Minyi (VerfasserIn) , Bérouti, Marleen (VerfasserIn) , Leonardi, Natascia (VerfasserIn) , Schillinger, Ulrike (VerfasserIn) , Holzmann, Bernhard (VerfasserIn) , Liesz, Arthur (VerfasserIn) , Roers, Axel (VerfasserIn) , Hölzel, Michael (VerfasserIn) , Basic, Marijana (VerfasserIn) , Wurst, Wolfgang (VerfasserIn) , Hornung, Veit (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: January 24, 2025
In: Journal of experimental medicine
Year: 2025, Jahrgang: 222, Heft: 3, Pages: 1-13
ISSN:1540-9538
DOI:10.1084/jem.20241424
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1084/jem.20241424
Verlag, kostenfrei, Volltext: https://rupress.org/jem/article/222/3/e20241424/277231/RNase-T2-restricts-TLR13-mediated-autoinflammation
Volltext
Verfasserangaben:Carlos Gomez-Diaz, Wilhelm Greulich, Benedikt Wefers, Meiyue Wang, Silvia Bolsega, Maike Effern, Daniel P. Varga, Zhe Han, Minyi Chen, Marleen Bérouti, Natascia Leonardi, Ulrike Schillinger, Bernhard Holzmann, Arthur Liesz, Axel Roers, Michael Hölzel, Marijana Basic, Wolfgang Wurst, and Veit Hornung
Beschreibung
Zusammenfassung:RNA-sensing TLRs are strategically positioned in the endolysosome to detect incoming nonself RNA. RNase T2 plays a critical role in processing long, structured RNA into short oligoribonucleotides that engage TLR7 or TLR8. In addition to its positive regulatory role, RNase T2 also restricts RNA recognition through unknown mechanisms, as patients deficient in RNase T2 suffer from neuroinflammation. Consistent with this, mice lacking RNase T2 exhibit interferon-dependent neuroinflammation, impaired hematopoiesis, and splenomegaly. However, the mechanism by which RNase T2 deficiency unleashes inflammation in vivo remains unknown. Here, we report that the inflammatory phenotype found in Rnaset2−/− mice is completely reversed in the absence of TLR13, suggesting aberrant accumulation of an RNA ligand for this receptor. Interestingly, this TLR13-driven inflammatory phenotype is also fully present in germ-free mice, suggesting a role for RNase T2 in limiting erroneous TLR13 activation by an as yet unidentified endogenous ligand. These results establish TLR13 as a potential self-sensor that is kept in check by RNase T2.
Beschreibung:Gesehen am 26.09.2025
Beschreibung:Online Resource
ISSN:1540-9538
DOI:10.1084/jem.20241424

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