期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 127, 期 7, 页码 2452-2463出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI90593
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资金
- Australian National Health and Medical Research Council (NHMRC) [APP1031728]
- National Cancer Institute [P01-CA142106-06A1, P01-CA047741-20]
- National Institute of Allergy and Infectious Diseases [P01-AI056299, R01-AI11879]
- Leukemia and Lymphoma Society Translational Research [6458-15, 6462-15]
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-beta 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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