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IL-22 deficiency in donor T cells attenuates murine acute graft-versus-host disease mortality while sparing the graft-versus-leukemia effect.

Abstract
Acute graft-versus-host disease (aGVHD) remains a major complication following allogeneic hematopoietic cell transplantation (allo-HCT), limiting the success of this therapy. Many proinflammatory cytokines secreted following the conditioning regimen have been linked to aGVHD initiation. Interleukin-22 (IL-22) is a cytokine related to IL-10 for its structure and is secreted by T helper type 17 (TH17) cells and innate immune cells. Given the paradoxical role of IL-22 in inflammation with both protective or proinflammatory functions, we investigated whether IL-22 could have a role in aGVHD pathophysiology in a mouse allo-HCT model. In this study, we show that IL-22 deficiency in donor T cells can decrease the severity of aGVHD, while limiting systemic and local inflammation in aGVHD target organs. In addition, we found that Foxp3+ regulatory T cells (Treg cells) were increased in recipient mice that received IL-22-deficient T cells, suggesting that Treg were involved in the reduced severity of GVHD. Finally, we found that the graft-versus-leukemia (GVL) effect mediated by donor T cells was preserved in the absence of IL-22. Overall, these data suggest that targeting of IL-22 may represent a valid approach towards decreasing aGVHD severity after allo-HCT while preserving the GVL effect.
AuthorsM Couturier, B Lamarthée, J Arbez, J-C Renauld, C Bossard, F Malard, F Bonnefoy, M Mohty, S Perruche, P Tiberghien, P Saas, B Gaugler
JournalLeukemia (Leukemia) Vol. 27 Issue 7 Pg. 1527-37 (Jul 2013) ISSN: 1476-5551 [Electronic] England
PMID23399894 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Inflammation Mediators
  • Interleukins
  • interleukin-22
Topics
  • Acute Disease
  • Adoptive Transfer
  • Animals
  • CD8-Positive T-Lymphocytes (immunology, metabolism)
  • Female
  • Forkhead Transcription Factors (metabolism)
  • Graft vs Host Disease (genetics, immunology, mortality)
  • Graft vs Leukemia Effect (immunology)
  • Hematopoietic Stem Cell Transplantation (methods, mortality)
  • Inflammation Mediators (immunology, metabolism)
  • Interleukins (genetics, immunology, metabolism)
  • Lymphoid Tissue (cytology, immunology)
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Severity of Illness Index
  • T-Lymphocytes, Regulatory (immunology, metabolism)

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