| First Author | Rai S | Year | 2022 |
| Journal | Nat Commun | Volume | 13 |
| Issue | 1 | Pages | 5346 |
| PubMed ID | 36100613 | Mgi Jnum | J:344212 |
| Mgi Id | MGI:7340833 | Doi | 10.1038/s41467-022-32927-4 |
| Citation | Rai S, et al. (2022) Inhibition of interleukin-1beta reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm. Nat Commun 13(1):5346 |
| abstractText | Interleukin-1beta (IL-1beta) is a master regulator of inflammation. Increased activity of IL-1beta has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1beta serum levels and expression of IL-1 receptors on hematopoietic progenitors and stem cells correlate with JAK2-V617F mutant allele fraction in peripheral blood of patients with MPN. We show that the source of IL-1beta overproduction in a mouse model of MPN are JAK2-V617F expressing hematopoietic cells. Knockout of IL-1beta in hematopoietic cells of JAK2-V617F mice reduces inflammatory cytokines, prevents damage to nestin-positive niche cells and reduces megakaryopoiesis, resulting in decrease of myelofibrosis and osteosclerosis. Inhibition of IL-1beta in JAK2-V617F mutant mice by anti-IL-1beta antibody also reduces myelofibrosis and osteosclerosis and shows additive effects with ruxolitinib. These results suggest that inhibition of IL-1beta with anti-IL-1beta antibody alone or in combination with ruxolitinib could have beneficial effects on the clinical course in patients with myelofibrosis. |
