| First Author | Hill GR | Year | 2010 |
| Journal | Blood | Volume | 116 |
| Issue | 5 | Pages | 819-28 |
| PubMed ID | 20435882 | Mgi Jnum | J:163508 |
| Mgi Id | MGI:4822120 | Doi | 10.1182/blood-2009-11-256495 |
| Citation | Hill GR, et al. (2010) Stem cell mobilization with G-CSF induces type 17 differentiation and promotes scleroderma. Blood 116(5):819-28 |
| abstractText | The recent shift to the use of stem cells mobilized by granulocyte colony-stimulating factor (G-CSF) for hematopoietic transplantation has increased chronic graftversus-host disease (GVHD), although the mechanisms of this are unclear. We have found that G-CSF invokes potent type 17 rather than type 1 or type 2 differentiation. The amplification of interleukin-17 (IL-17) production by G-CSF occurs in both CD4 and CD8 conventional T cells and is dependent on, and downstream of, G-CSF-induced IL-21 signaling. Importantly, donor IL-17A controls the infiltration of macrophages into skin and cutaneous fibrosis, manifesting late after transplantation as scleroderma. Interestingly, donor CD8 T cells were the predominant source of IL-17A after transplantation and could mediate scleroderma independently of CD4 T cells. This study provides a logical explanation for the propensity of allogeneic stem cell transplantation to invoke sclerodermatous GVHD and suggests a therapeutic strategy for intervention. |
