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Cytokine mediators of chronic graft-versus-host disease.


ABSTRACT: 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-? secretion, respectively, leading to fibrosis. This new understanding permits the design of rational cytokine and intracellular signaling pathway-targeted therapeutics, reviewed herein.

SUBMITTER: MacDonald KP 

PROVIDER: S-EPMC5490762 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Cytokine mediators of chronic graft-versus-host disease.

MacDonald Kelli Pa KP   Blazar Bruce R BR   Hill Geoffrey R GR  

The Journal of clinical investigation 20170630 7


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 inc  ...[more]

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