| First Author | Lin FC | Year | 2014 |
| Journal | Blood | Volume | 124 |
| Issue | 25 | Pages | 3699-708 |
| PubMed ID | 25342713 | Mgi Jnum | J:220784 |
| Mgi Id | MGI:5636129 | Doi | 10.1182/blood-2014-01-549527 |
| Citation | Lin FC, et al. (2014) IFN-gamma causes aplastic anemia by altering hematopoietic stem/progenitor cell composition and disrupting lineage differentiation. Blood 124(25):3699-708 |
| abstractText | Aplastic anemia (AA) is characterized by hypocellular marrow and peripheral pancytopenia. Because interferon gamma (IFN-gamma) can be detected in peripheral blood mononuclear cells of AA patients, it has been hypothesized that autoreactive T lymphocytes may be involved in destroying the hematopoietic stem cells. We have observed AA-like symptoms in our IFN-gamma adenylate-uridylate-rich element (ARE)-deleted (del) mice, which constitutively express a low level of IFN-gamma under normal physiologic conditions. Because no T-cell autoimmunity was observed, we hypothesized that IFN-gamma may be directly involved in the pathophysiology of AA. In these mice, we did not detect infiltration of T cells in bone marrow (BM), and the existing T cells seemed to be hyporesponsive. We observed inhibition in myeloid progenitor differentiation despite an increase in serum levels of cytokines involved in hematopoietic differentiation and maturation. Furthermore, there was a disruption in erythropoiesis and B-cell differentiation. The same phenomena were also observed in wild-type recipients of IFN-gamma ARE-del BM. The data suggest that AA occurs when IFN-gamma inhibits the generation of myeloid progenitors and prevents lineage differentiation, as opposed to infiltration of activated T cells. These results may be useful in improving treatment as well as maintaining a disease-free status. |
