Open AccessGM-CSF–Responsive Monocyte-Derived Dendritic Cells Are Pivotal in Th17 Pathogenesis
Author(s) -
HyunJa Ko,
Jamie L. Brady,
Victoria Ryg-Cornejo,
Diana S. Hansen,
David Vremec,
Ken Shortman,
Yifan Zhan,
Andrew M. Lew
Publication year - 2014
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.1302040
Subject(s) - in vivo , dendritic cell , immunology , inflammation , microbiology and biotechnology , ccr2 , in vitro , interleukin 23 , plasmacytoid dendritic cell , monocyte , biology , interleukin 17 , chemistry , immune system , chemokine , chemokine receptor , genetics
Although multiple dendritic cell (DC) subsets have the potential to induce Th17 differentiation in vitro, the key DC that is critical in Th17 induction and Th17-mediated disease remains moot. In this study, we revealed that CCR2(+) monocyte-derived DCs (moDCs), but not conventional DCs, were critical for in vivo Th17 induction and autoimmune inflammation. Functional comparison in vitro indicated that moDCs are the most potent type of Th17-inducing DCs compared with conventional DCs and plasmacytoid DCs. Furthermore, we demonstrated that the importance of GM-CSF in Th17 induction and Th17-mediated disease is its endowment of moDCs to induce Th17 differentiation in vivo, although it has little effect on moDC numbers. Our findings identify the in vivo cellular targets that can be selectively manipulated to ameliorate Th17-mediated inflammatory diseases, as well as the mechanism of GM-CSF antagonism in such diseases.
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