| First Author | Bucher C | Year | 2009 |
| Journal | Blood | Volume | 114 |
| Issue | 26 | Pages | 5375-84 |
| PubMed ID | 19843883 | Mgi Jnum | J:155701 |
| Mgi Id | MGI:4415111 | Doi | 10.1182/blood-2009-05-221135 |
| Citation | Bucher C, et al. (2009) IL-21 blockade reduces graft-versus-host disease mortality by supporting inducible T regulatory cell generation. Blood 114(26):5375-84 |
| abstractText | Interleukin-21 (IL-21) enhances T helper 1 (Th1) and Th17 differentiation while inhibiting the conversion of inducible regulatory T cells (Tregs) from naive T cells. To determine the role of IL-21 in graft-versus-host disease (GVHD), anti-IL-21 antibody (Ab) was given to recipients of CD25(-)CD4(+) or CD4(+) and CD8(+) T-effectors. IL-21 neutralization attenuated GVHD-related weight loss and prolonged survival. Likewise, a majority of mice receiving IL-21(-/-) CD25(-) T-effectors survived long term, whereas those receiving wild-type T cells died. The latter recipients had higher grades of GVHD in the ileum and colon. Surprisingly, disruption of IL-21 signaling did not affect IL-17 production, although colon-infiltrating T-effector cells had decreased interferon gamma (IFNgamma) and increased IL-4 production. FoxP3(+) Tregs were increased in colons of anti-IL-21 Ab-treated recipients of FoxP3(-) IL-21(-/-) T cells, indicating Treg conversion. Recipients of FoxP3-deficient T-effectors isolated from chimeras were resistant to the GVHD protective effects of IL-21 blockade. Whereas graft-versus-leukemia (GVL) can occur in the absence of IL-21, loss of both IL-21 and perforin expression abrogated GVL. Together, these data indicate that IL-21 suppresses inducible Treg conversion and further suggest that IL-21 blockade is an attractive strategy to reduce GVHD-induced injury. |
