IL-22 promoted CD3+ T cell infiltration by IL-22R induced STAT3 phosphorylation in murine acute graft versus host disease target organs after allogeneic bone marrow transplantation

Int Immunopharmacol. 2016 Oct:39:383-388. doi: 10.1016/j.intimp.2016.08.012. Epub 2016 Aug 20.

Abstract

Graft versus host disease (GVHD) is a life threatening complication of bone marrow stem cell transplantation, in which considerable numbers of proinflammatory cytokines secreted by allo-reactive donor T cells are involved. We and other previous studies have found that interleukin-22 (IL-22) was able to aggravate the target organs damage of GVHD. However, the mechanism and the signal pathway of IL-22 in murine acute GVHD was not clear. Here, we observed that compared with GVHD group, more serious pathological damage and more CD3(+) T cells infiltrated in GVHD target organs were detected in the mice injected with IL-22. Meanwhile, transcription factor T-bet, RORγt and AhR respectively associated with Th1, Th17 and Th22 cells changed in varying degrees in different GVHD target organs. Furthermore, the increased expression of IL-22R and its downstream protein P-STAT3 were detected in GVHD mice with IL-22 treated. These results suggested that the pathological role of IL-22 in GVHD target organs contribute to exogenous injected IL-22 as well as secreted IL-22 from the infiltrated allo-reactive effector T cells. In addition, the IL-22R-STAT3 pathway may play important role in GVHD tissue injury and target this way may yield new approaches for reduction of GVHD.

Keywords: Allo-BMT; IL-22; T cell; aGVHD.

MeSH terms

  • Acute Disease
  • Animals
  • Bone Marrow Transplantation*
  • CD3 Complex / metabolism
  • Cell Movement
  • Cells, Cultured
  • Graft vs Host Disease / immunology*
  • Interleukin-22
  • Interleukins / immunology*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Phosphorylation
  • Receptors, Interleukin / metabolism*
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction
  • T-Lymphocytes / immunology*
  • Transplantation, Homologous

Substances

  • CD3 Complex
  • Interleukins
  • Receptors, Interleukin
  • STAT3 Transcription Factor
  • Stat3 protein, mouse
  • interleukin-22 receptor