Cytokine mediators of chronic graft-versus-host disease
Kelli P.A. MacDonald,1 Bruce R. Blazar,2 and Geoffrey R. Hill3,4
1Antigen Presentation and Immunoregulation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
2Masonic Cancer Center; and Division of Blood and Marrow Transplantation, Department of Pediatrics; University of Minnesota, Minneapolis, USA.
3Bone Marrow Transplantation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
4Royal Brisbane and Women’s Hospital, Brisbane, Australia.
Address correspondence to: Kelli P.A. MacDonald, Antigen Presentation and Immunoregulation Laboratory, 300 Herston Road, Herston, Queensland 4006, Australia. Phone: 61.7.3362.0404; Email: kelli.macdonald@qimrberghofer.edu.au. Or to: Geoffrey R. Hill, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia. Phone: 61.7.3845.3763; Email: Geoff.Hill@qimrberghofer.edu.au. Or to: Bruce R. Blazar, University of Minnesota, Department of Pediatrics, Division of Blood and Marrow Transplantation, MMC 109, 420 SE Delaware Street, Minneapolis, Minnesota 55455, USA. Phone: 612.626.1926; Email: blaza001@umn.edu.
Authorship note: B.R. Blazar and G.R. Hill contributed equally to this work.
Find articles by MacDonald, K. in: JCI | PubMed | Google Scholar
1Antigen Presentation and Immunoregulation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
2Masonic Cancer Center; and Division of Blood and Marrow Transplantation, Department of Pediatrics; University of Minnesota, Minneapolis, USA.
3Bone Marrow Transplantation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
4Royal Brisbane and Women’s Hospital, Brisbane, Australia.
Address correspondence to: Kelli P.A. MacDonald, Antigen Presentation and Immunoregulation Laboratory, 300 Herston Road, Herston, Queensland 4006, Australia. Phone: 61.7.3362.0404; Email: kelli.macdonald@qimrberghofer.edu.au. Or to: Geoffrey R. Hill, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia. Phone: 61.7.3845.3763; Email: Geoff.Hill@qimrberghofer.edu.au. Or to: Bruce R. Blazar, University of Minnesota, Department of Pediatrics, Division of Blood and Marrow Transplantation, MMC 109, 420 SE Delaware Street, Minneapolis, Minnesota 55455, USA. Phone: 612.626.1926; Email: blaza001@umn.edu.
Authorship note: B.R. Blazar and G.R. Hill contributed equally to this work.
Find articles by Blazar, B. in: JCI | PubMed | Google Scholar
1Antigen Presentation and Immunoregulation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
2Masonic Cancer Center; and Division of Blood and Marrow Transplantation, Department of Pediatrics; University of Minnesota, Minneapolis, USA.
3Bone Marrow Transplantation Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Australia.
4Royal Brisbane and Women’s Hospital, Brisbane, Australia.
Address correspondence to: Kelli P.A. MacDonald, Antigen Presentation and Immunoregulation Laboratory, 300 Herston Road, Herston, Queensland 4006, Australia. Phone: 61.7.3362.0404; Email: kelli.macdonald@qimrberghofer.edu.au. Or to: Geoffrey R. Hill, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Queensland 4006, Australia. Phone: 61.7.3845.3763; Email: Geoff.Hill@qimrberghofer.edu.au. Or to: Bruce R. Blazar, University of Minnesota, Department of Pediatrics, Division of Blood and Marrow Transplantation, MMC 109, 420 SE Delaware Street, Minneapolis, Minnesota 55455, USA. Phone: 612.626.1926; Email: blaza001@umn.edu.
Authorship note: B.R. Blazar and G.R. Hill contributed equally to this work.
Find articles by Hill, G. in: JCI | PubMed | Google Scholar
First published June 30, 2017 - More info
J Clin Invest. 2017;127(7):2452–2463. doi:10.1172/JCI90593.
Copyright © 2017, American Society for Clinical Investigation
Substantial preclinical and clinical research into chronic graft-versus-host disease (cGVHD) has come to fruition in the last five years, generating a clear understanding of a complex cytokine-driven cellular network. cGVHD is mediated by naive T cells differentiating within IL-17–secreting T cell and follicular Th cell paradigms to generate IL-21 and IL-17A, which drive pathogenic germinal center (GC) B cell reactions and monocyte-macrophage differentiation, respectively. cGVHD pathogenesis includes thymic damage, impaired antigen presentation, and a failure in IL-2–dependent Treg homeostasis. Pathogenic GC B cell and macrophage reactions culminate in antibody formation and TGF-β secretion, respectively, leading to fibrosis. This new understanding permits the design of rational cytokine and intracellular signaling pathway–targeted therapeutics, reviewed herein.
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ISSN: 0021-9738 (print), 1558-8238 (online)