| First Author | He H | Year | 2020 |
| Journal | Blood | Volume | 136 |
| Issue | 2 | Pages | 183-198 |
| PubMed ID | 32305041 | Mgi Jnum | J:301309 |
| Mgi Id | MGI:6503701 | Doi | 10.1182/blood.2019003910 |
| Citation | He H, et al. (2020) Aging-induced IL27Ra signaling impairs hematopoietic stem cells. Blood 136(2):183-198 |
| abstractText | Hematopoietic stem cell (HSC) aging correlates with an increasing risk of myeloproliferative disease and immunosenescence. In this study, we show that aging-related inflammation promotes HSC aging through tumor necrosis factor-alpha (TNF-alpha)-->ERK-->ETS1-->interleukin27Ra (IL27Ra) pathway. TNF-alpha, a well-known biomarker of inflammation, increases during aging and induces the expression of IL27Ra on HSCs via ERK-ETS1 signaling. Deletion of IL27Ra rescues the functional decline and myeloid bias of HSCs and also reverses the inhibitory effect of TNF-alpha on HSCs. Aged IL27Ra-/- mice had a reduced proportion of myeloid-biased HSCs and did not display the biased myeloid differentiation that occurs in aged wild-type mice. IL27Ra+ HSCs exhibit impaired reconstitution capacity and myeloid-bias compared with IL27Ra- HSCs and serve as a myeloid-recovery pool upon inflammatory insult. Inflammation-related genes were enriched in IL27Ra+ HSCs and this enrichment increases with aging. Our study demonstrates that age-induced IL27Ra signaling impairs HSCs and raises the possibility that interfering with IL27Ra signaling can counter the physiologically deleterious effect of aging on hematopoietic capacity. |
