Effect of IL-22 on intestinal stem cells, GVHD-related tissue damage, and GVL.

6539 Background: Intestinal graft vs. host disease (GVHD) is a major complication of allogeneic bone marrow transplantation (allo-BMT). Strategies to limit GVHD by selective promotion of epithelial regeneration in the absence of immunosuppression are largely unknown. Methods: We investigated the role of IL-22 in allo-BMT by utilizing wild type and IL-22 knockout (KO) mice as donors or recipients in allo-BMT. Results: We found that administration of an anti-IL-22 neutralizing antibody to allo-BMT recipients during the first month post-BMT led to increased GVHD mortality, indicating that IL-22 functioned to reduce GVHD severity post-BMT. In contrast, use of IL-22 KO donor T cells did not impair their ability to eliminate A20 lymphoma cells upon tumor challenge, thus indicating that IL-22 was not essential for donor T cells to mediate graft vs. lymphoma (GVL) responses. BMT with WT donors and recipients indicated that IL-22 levels in small and large intestine were increased after BMT and after radiation inju...