| First Author | Wu Z | Year | 2019 |
| Journal | Exp Hematol | Volume | 69 |
| Pages | 54-64.e2 | PubMed ID | 30316805 |
| Mgi Jnum | J:318530 | Mgi Id | MGI:6860027 |
| Doi | 10.1016/j.exphem.2018.10.003 | Citation | Wu Z, et al. (2019) Interleukin-18 plays a dispensable role in murine and likely also human bone marrow failure. Exp Hematol 69:54-64.e2 |
| abstractText | Interleukin-18 (IL-18), also known as interferon-gamma (IFN-gamma)-inducing factor, is involved in Th1 responses and regulation of immunity. Accumulating evidence implicates IL-18 in autoimmune diseases, but little is known of its role in acquired aplastic anemia (AA), the immune-mediated destruction of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs). IL-18 protein levels were significantly elevated in sera of severe AA (SAA) patients, including both responders and nonresponders assayed before treatment, and decreased after treatment. IL-18 receptor (IL-18R) was expressed on HSPCs. Co-culture of human BM CD34(+) cells from healthy donors with IL-18 upregulated genes in the helper T-cell and Notch signaling pathways and downregulated genes in the cell cycle regulation, telomerase, and IL-6 signaling pathways. Plasma IL-18 levels were also elevated in murine models of immune-mediated BM failure. However, deletion of IL-18 in donor lymph node cells or deletions of either IL-18 or IL-18R in recipients did not attenuate elevations of circulating IFN-gamma, tumor necrosis factor-alpha, or IL-6, nor did they alleviate BM failure. In summary, our findings suggest that, although increased circulating IL-18 is a feature of SAA, it may reflect an aberrant immune response but be dispensable to the pathogenesis of AA. |
