title: The expression of Th17-associated cytokines in human acute graft-versus-host disease.
abstract: The role of Th17 cells and Th17-associated cytokines in the development of acute graft-versus-host disease (aGVHD) in clinical allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients is not well established. In the current study, a cohort of 69 allo-HSCT patients was examined for the percentages of Th17 and FoxP3(+) Treg cells and the expressions of RORγt and FoxP3 in peripheral blood mononuclear cells (PBMCs). The Th17 percentage and RORγt expression were significantly higher, whereas Treg percentage and FoxP3 expression were significantly lower in severe aGVHD (grade 3 to 4) and mild aGVHD (grade 1 to 2) patients than in patients without aGVHD (grade 0) and healthy donors. We then investigated the expressions of Th17-associated cytokines, including TGF-β, IL-6, IL-1β, IL-17, IL-21, IL-22, IL-23, as well as IL-23R in the PBMCs of patients after allo-HSCT. The expressions of IL-17 and IL-22 in CD4(+) T cells were also examined. The results showed that the expressions of IL-6, IL-1β, IL-17, IL-21, IL-23, and IL-23R were all increased, whereas IL-22 expression was decreased in aGVHD patients. The changes were also correlated with the severity of aGVHD. We also investigated the dynamic changes of Th17/Treg cells and Th17-associated cytokines in patients during the onset and resolution of aGVHD. The results demonstrated a reciprocal relationship between Treg and Th17 cells. Th17-associated cytokine expressions, namely IL-17 and IL-23, were closely related to the occurrence and resolution of aGVHD. We conclude that the dynamic balance between the Th17 and FoxP3(+) Treg cells and the changes of Th17-associated cytokines could be the indicators of the disease progression and promising candidates of prognostic biomarkers of aGVHD.
authors.affiliation: Laboratory of Cellular and Molecular Tumor Immunology, Cyrus Tang Hematology Center, Department of Hematology, The First Affiliated Hospital of Soochow University, Jiangsu Institute of Hematology and Key Laboratory of Thrombosis and Hemostasis Ministry of Health, Suzhou, China.
authors.forename: Yuejun
authors.initials: Y
authors.lastname: Liu
authors.forename: Yifeng
authors.initials: Y
authors.lastname: Cai
authors.forename: Lan
authors.initials: L
authors.lastname: Dai
authors.forename: Guanghua
authors.initials: G
authors.lastname: Chen
authors.forename: Xiao
authors.initials: X
authors.lastname: Ma
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Xu
authors.forename: Song
authors.initials: S
authors.lastname: Jin
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Wu
authors.forename: Huiying
authors.initials: H
authors.lastname: Qiu
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Tang
authors.forename: Caixia
authors.initials: C
authors.lastname: Li
authors.forename: Aining
authors.initials: A
authors.lastname: Sun
authors.forename: Depei
authors.initials: D
authors.lastname: Wu
authors.forename: Haiyan
authors.initials: H
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D002648:Child; D016207:Cytokines / Q000096:biosynthesis* / Q000097:blood / Q000276:immunology; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D058504:Th17 Cells / Q000276:immunology*; D019172:Transplantation Conditioning / Q000379:methods*; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D016207:Cytokines
keywords: Acute graft-versus-host disease; Allogeneic hematopoietic cell transplantation; Regulatory T cells; Th17 cells