Absence of IL-23p19 in donor allogeneic cells reduces mortality from acute GVHD
- 31 August 2009
- journal article
- Published by Springer Science and Business Media LLC in Bone Marrow Transplantation
- Vol. 45 (4), 712-722
- https://doi.org/10.1038/bmt.2009.215
Abstract
The p19 dimer of interleukin 23 (IL-23) has been reported to have a major role in the pathogenesis of many experimental and clinical autoimmune diseases and may also have a prominent role in transplantation. We reasoned that deficiency of p19 in the allogeneic donor transplant might reduce the inflammation caused by acute GVHD (aGVHD). The major histocompatibility complex-2 (H2d) BALB/c mice were subjected to 8.5 Gy TBI, followed by transplantation with 10 × 106 BM and 2.5 × 106 spleen cells from H2d BALB/c, H2b C57Bl/6 (B6) or H2b p19−/− donors. In all, 75% of the p19−/− transplanted mice survived, compared with only 12.5% of the B6 transplanted mice. This superior survival is correlated with significantly less severe aGVHD, absence of p19 after transplantation, less upregulation of mRNA and lower serum levels of IL-17 as compared with the B6 transplants. TBI alone significantly upregulated transforming growth factor-β (TGF-β), IL-6 and p19 mRNA levels in host BALB/c mice, possibly providing the milieu to induce IL-17 in p19−/− donor cells. IL-22, another cytokine, the induction of which in T-helper 17 (Th17) cells is supported by p19, was upregulated in BALB/c hosts but not in transplanted B6 or p19 donor cells, and may not have had a major role in modifying aGVHD.Keywords
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