LAUSR

HighlightsKnock out of IL‐22 in recipients aggravates hepatic and intestinal aGVHD.IL‐22 mediates activation of dendritic cells.Recipient‐derived IL‐22 regulates polarization of Th1 cells and Tregs in aGVHD. Abstract Acute graft‐versus‐host disease (aGVHD) remains a major challenging complication of patients receiving allogeneic hematopoietic cell transplantation (allo‐HCT). CD4+ effector T cells and their related cytokines mediate pathogenesis of aGVHD, in which donor‐T‐cell derived interleukin‐22 (IL‐22) was recently indicated to play a role. The role of recipient‐derived IL‐22 in aGVHD remains to be elucidated. By applying IL‐22 knock out (IL‐22KO) mice as recipients of allotransplant, we found recipient derived IL‐22 alleviated aGVHD and improved survival of allotransplant recipients. Knock out of IL‐22 in recipient increased levels of T‐helper (Th1) 1 cells but decreased levels of regulatory T cells (Tregs) in target tissues of aGVHD. Levels of IL‐22 increased in aGVHD mice. Recipient antigen presenting cells (APCs) are important sources of IL‐22. IL‐22 reduced activation of APCs in vitro. Defect of IL‐22 in APCs resulted in increased polarization of Th1 cells but decreased level of Tregs in an in vitro co‐culture system. Our data highlight an immunoregulatory function of recipient‐derived IL‐22 in aGVHD.