title: 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.
authors: INSERM UMR1098, Besançon, France.
authors: M
authors: M
authors: Couturier
authors: B
authors: B
authors: Lamarthée
authors: J
authors: J
authors: Arbez
authors: J-C
authors: JC
authors: Renauld
authors: C
authors: C
authors: Bossard
authors: F
authors: F
authors: Malard
authors: F
authors: F
authors: Bonnefoy
authors: M
authors: M
authors: Mohty
authors: S
authors: S
authors: Perruche
authors: P
authors: P
authors: Tiberghien
authors: P
authors: P
authors: Saas
authors: B
authors: B
authors: Gaugler
mesh_terms: D000208:Acute Disease; D019264:Adoptive Transfer; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology / Q000401:mortality; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods / Q000401:mortality*; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D012720:Severity of Illness Index; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D000097043:Interleukin-22
chemical_list: D051858:Forkhead Transcription Factors; D018836:Inflammation Mediators; D007378:Interleukins; D000097043:Interleukin-22; C498833:Foxp3 protein, mouse