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.
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Acknowledgements
We thank the technical support of D. Paris for animal care. We also thank the ‘Association pour la Recherche sur le Cancer (ARC; Grant No.3175 to MM and BG)’, the ‘Agence de Biomédecine’, the ‘Association Cent pour Sang la Vie’, the Conseil Régional de Franche-Comté (AutoMACS Pro), the Agence Nationale de la Recherche (Labex LipSTIC, ANR-11-LABX-0021) and the Etablissement Français du Sang (AO#2011-11) for their generous and continuous support for our research work.
Author contributions
All authors listed in the manuscript have contributed substantially to this work. BG designed experimental research, interpreted data and wrote the manuscript; MC and BL participated in experimental design, performed research, analyzed data and wrote the manuscript; JA, FB and SP participated in experimental work; JCR generated IL-22-deficient mice; FM and CB performed histological analyses; MM, PS and PT participated in experimental design, interpretation of data and helped in writing and revising the manuscript.
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Couturier, M., Lamarthée, B., Arbez, J. et al. IL-22 deficiency in donor T cells attenuates murine acute graft-versus-host disease mortality while sparing the graft-versus-leukemia effect. Leukemia 27, 1527–1537 (2013). https://doi.org/10.1038/leu.2013.39
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DOI: https://doi.org/10.1038/leu.2013.39
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