Cytokine mediators of chronic graft-versus-host disease

Kelli P.A. MacDonald, Bruce R. Blazar, Geoffrey R. Hill

Research output: Contribution to journalReview articlepeer-review

65 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)2452-2463
Number of pages12
JournalJournal of Clinical Investigation
Issue number7
StatePublished - Jun 30 2017


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