| First Author | Igarashi K | Year | 2022 |
| Journal | Exp Hematol | Volume | 106 |
| Pages | 47-57 | PubMed ID | 34808257 |
| Mgi Jnum | J:319784 | Mgi Id | MGI:6865437 |
| Doi | 10.1016/j.exphem.2021.11.006 | Citation | Igarashi K, et al. (2022) CCL8 deficiency in the host abrogates early mortality of acute graft-versus-host disease in mice with dysregulated IL-6 expression. Exp Hematol 106:47-57 |
| abstractText | Although allogeneic hematopoietic stem cell transplantation (HSCT) is a curative treatment for diverse malignant and nonmalignant diseases, acute graft-versus-host disease (aGVHD) is strongly linked to mortality caused by HSCT. We previously reported that CC chemokine ligand 8 (CCL8) is closely correlated to aGVHD mortality in both humans and mice. To study the role of CCL8 in aGVHD, CCL8 knockout (CCL8(-/-)) mice were transplanted with fully allogeneic marrow grafts. These mice exhibited a significant reduction in mortality (90.0% vs. 23.4% survival for CCL8(-/-) vs. wild-type recipients at day 28, p < 0.0001). As a result, apparent prolonged median survival from 9 days in wild-type mice to 45 days in CCL8(-/-) mice was observed. Acute GVHD pathology and liver dysfunction in CCL8(-/-) mice were significantly attenuated compared with those in wild-type mice. In association with the reduced mortality, a surge of plasma interleukin (IL)-6 was observed in CCL8(-/-) recipients with allogeneic marrow, which was significantly increased compared with wild-type mice that received allografts. Donor T-cell expansion and plasma levels of interferon-gamma and TNF-alpha during aGVHD were similar in both types of mice. Collectively, these findings indicate that CCL8 plays a major role in aGVHD pathogenesis with possible involvement of an IL-6 signaling cascade. |
