TY - JOUR
T1 - Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3
AU - Von Gamm, Matthias
AU - Schaub, Annalisa
AU - Jones, Alisha N.
AU - Wolf, Christine
AU - Behrens, Gesine
AU - Lichti, Johannes
AU - Essig, Katharina
AU - Macht, Anna
AU - Pircher, Joachim
AU - Ehrlich, Andreas
AU - Davari, Kathrin
AU - Chauhan, Dhruv
AU - Busch, Benjamin
AU - Wurst, Wolfgang
AU - Feederle, Regina
AU - Feuchtinger, Annette
AU - Tschöp, Matthias H.
AU - Friedel, Caroline C.
AU - Hauck, Stefanie M.
AU - Sattler, Michael
AU - Geerlof, Arie
AU - Hornung, Veit
AU - Heissmeyer, Vigo
AU - Schulz, Christian
AU - Heikenwalder, Mathias
AU - Glasmacher, Elke
N1 - Publisher Copyright:
© 2019 von Gamm et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
PY - 2019
Y1 - 2019
N2 - The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-κB signaling. The roles of its family members, however, remain largely unknown. Here, we analyzed Regnase-3–deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell–specific deletions of Regnase-3 to demonstrate that Regnase-3 acts specifically within myeloid cells. Regnase-3 deficiency systemically increased IFN signaling, which increased the proportion of immature B and innate immune cells, and suppressed follicle and germinal center formation. Expression analysis revealed that Regnase-3 and Regnase-1 share protein degradation pathways. Unlike Regnase-1, Regnase-3 expression is high specifically in macrophages and is transcriptionally controlled by IFN signaling. Although direct targets in macrophages remain unknown, Regnase-3 can bind, degrade, and regulate mRNAs, such as Zc3h12a (Regnase-1), in vitro. These data indicate that Regnase-3, like Regnase-1, is an RNase essential for immune homeostasis but has diverged as key regulator in the IFN pathway in macrophages.
AB - The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-κB signaling. The roles of its family members, however, remain largely unknown. Here, we analyzed Regnase-3–deficient mice, which develop hypertrophic lymph nodes. We used various mice with immune cell–specific deletions of Regnase-3 to demonstrate that Regnase-3 acts specifically within myeloid cells. Regnase-3 deficiency systemically increased IFN signaling, which increased the proportion of immature B and innate immune cells, and suppressed follicle and germinal center formation. Expression analysis revealed that Regnase-3 and Regnase-1 share protein degradation pathways. Unlike Regnase-1, Regnase-3 expression is high specifically in macrophages and is transcriptionally controlled by IFN signaling. Although direct targets in macrophages remain unknown, Regnase-3 can bind, degrade, and regulate mRNAs, such as Zc3h12a (Regnase-1), in vitro. These data indicate that Regnase-3, like Regnase-1, is an RNase essential for immune homeostasis but has diverged as key regulator in the IFN pathway in macrophages.
UR - https://www.scopus.com/pages/publications/85069266271
U2 - 10.1084/jem.20181762
DO - 10.1084/jem.20181762
M3 - Article
C2 - 31126966
AN - SCOPUS:85069266271
SN - 0022-1007
VL - 216
SP - 1700
EP - 1723
JO - Journal of Experimental Medicine
JF - Journal of Experimental Medicine
IS - 7
ER -