1. Cytokine mediators of chronic graft-versus-host disease.
- Author
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MacDonald, Kelli P. A., Blazar, Bruce R., Hill, Geoffrey R., and MacDonald, Kelli Pa
- Subjects
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GRAFT versus host disease , *CYTOKINES , *T cells , *INTERLEUKIN-2 , *HOMEOSTASIS , *ANIMAL experimentation , *B cells , *CELLULAR signal transduction , *CHRONIC diseases , *LYMPHOID tissue , *MACROPHAGES , *RESEARCH funding , *THERAPEUTICS - 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-β secretion, respectively, leading to fibrosis. This new understanding permits the design of rational cytokine and intracellular signaling pathway-targeted therapeutics, reviewed herein. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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