Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3.
J Exp Med
; 216(7): 1700-1723, 2019 07 01.
Article
em En
| MEDLINE
| ID: mdl-31126966
ABSTRACT
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Ribonucleases
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Interferons
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Células Mieloides
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Homeostase
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Imunidade Inata
Limite:
Animals
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article