| First Author | von Gamm M | Year | 2019 |
| Journal | J Exp Med | Volume | 216 |
| Issue | 7 | Pages | 1700-1723 |
| PubMed ID | 31126966 | Mgi Jnum | J:277714 |
| Mgi Id | MGI:6342363 | Doi | 10.1084/jem.20181762 |
| Citation | von Gamm M, et al. (2019) Immune homeostasis and regulation of the interferon pathway require myeloid-derived Regnase-3. J Exp Med 216(7):1700-1723 |
| abstractText | The RNase Regnase-1 is a master RNA regulator in macrophages and T cells that degrades cellular and viral RNA upon NF-kappaB 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. |
