Absence of IL-23p19 in donor allogeneic cells reduces mortality from acute GVHD

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 de. ciency of p19 in the allogeneic donor transplant might reduce the in. ammation caused by acute GVHD (aGVHD). The major histocompatibility complex2 (H2(d)) BALB/c mice were subjected to 8.5 Gy TBI, followed by transplantation with 10 x 10(6) BM and 2.5 x 10(6) spleen cells from H2(d) BALB/c, H2(b) C57Bl/6 (B6) or H2(b) 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 signi. cantly 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 signi. cantly upregulated transforming growth factor-beta (TGF-beta), 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. Bone Marrow Transplantation (2010) 45, 712-722; doi:10.1038/bmt.2009.215; published online 31 August 2009