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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Authors | M Couturier, B Lamarthée, J Arbez, J-C Renauld, C Bossard, F Malard, F Bonnefoy, M Mohty, S Perruche, P Tiberghien, P Saas, B Gaugler |
Journal | Leukemia
(Leukemia)
Vol. 27
Issue 7
Pg. 1527-37
(Jul 2013)
ISSN: 1476-5551 [Electronic] England |
PMID | 23399894
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Forkhead Transcription Factors
- Foxp3 protein, mouse
- Inflammation Mediators
- Interleukins
- interleukin-22
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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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