G-CSF induces a potentially tolerant gene and immunophenotype profile in T cells in vivo.
G-CSF can induce functional immune tolerance in man. In this study, purified T cells from G-CSF-mobilized peripheral blood stem cell (PBSC) donors were analysed by gene expression profiling and immunophenotyping. Results suggested a predominantly immune tolerant profile with upregulation of genes related to Th2 and Treg cells, downregulation of genes associated with Th1 cells, cytotoxicity, antigen presentation and graft-versus-host disease (GVHD) and overexpression of negative regulators of Th17 differentiation. Immunophenotyping revealed that during G-CSF exposure donors had reduced levels of T cells with a Th17 phenotype (CD4+IL-17A+CCR6+IL-23R+), more than three times lower compared to normal controls. G-CSF also led to increased levels of CD4+CD25highCD45RO+ Treg cells. Furthermore, mRNA levels of RORgammat, a Th17-specific transcription factor, decreased in T cells isolated from G-CSF-mobilized PBSC harvests. Th17 cells have been implicated in autoimmune diseases and GVHD pathophysiology. Our study is the first to report the effect of G-CSF on the Th17 subpopulation.
Toh, HC; Sun, L; Soe, Y; Wu, Y; Phoon, YP; Chia, WK; Wu, J; Wong, KY; Tan, P
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