Interleukin-22 aggravates murine acute graft-versus-host disease by expanding effector T cell and reducing regulatory T cell.

Abstract

Graft-versus-host disease (GVHD) as a major complication after allogeneic hematopoietic stem cell transplantation is not well prevented now. We have observed that interleukin-22 (IL-22) produced by Th22, Th1, and Th17 cells participated in GVHD development in our previous study. However, the role of IL-22 in GVHD is still ambiguous. The aim of this study was to illuminate the pathological or protective function and the potential mechanism of IL-22 in the GVHD process. In the present study, we found that compared with mice cotransferred with bone marrow and spleen cells (BS mice) without IL-22 administration, more serious tissue damage and higher GVHD clinical score were observed in BS+IL-22 mice. IL-22 administration was a benefit to early recovery of thymus after irradiation-induced injury. Administration of IL-22 could promote Th1 and Tc1 cell expansion in mesenteric lymph nodes but reduce CD4(+)CD25(+)Foxp3(+) regulatory T (Treg) cell number. Levels of systemic inflammatory cytokines (IFN-γ and TNF-α) were upregulated, while the level of immunosuppressive cytokine IL-10 was downregulated in recipients with IL-22 injection. In conclusion, IL-22, which exacerbates both local immune responses and systemic inflammation of recipients, plays a pathogenic role in the GVHD process. The potential mechanism of IL-22 in GVHD may attribute to increased alloreactive effector Th1 and Tc1 cells and decreased inhibitory Treg cell.

• Authors: Kai Zhao, Dongmei Zhao, Dong Huang, Lingling Yin, Chong Chen, Bin Pan, Qingyun Wu, Zhenyu Li, Yao Yao, Erxia Shen, Lingyu Zeng, Kailin Xu
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 34 Issue 9 Pg. 707-15 (Sep 2014) ISSN: 1557-7465 [Electronic] United States
• PMID: 24720737 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukins
• Tumor Necrosis Factor-alpha
• Interferon-gamma
• interleukin-22

Topics

• Animals
• Bone Marrow Cells (immunology)
• Down-Regulation (immunology)
• Graft vs Host Disease (immunology)
• Interferon-gamma (immunology)
• Interleukins (genetics, immunology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Spleen (immunology)
• T-Lymphocytes, Regulatory (immunology)
• Th1 Cells (immunology)
• Th17 Cells (immunology)
• Tumor Necrosis Factor-alpha (immunology)
• Up-Regulation (immunology)