IL-17 is a potent synergistic factor with GM-CSF in mice in stimulating myelopoiesis, dendritic cell expansion, proliferation, and functional enhancement.
OBJECTIVE
Interleukin (IL)-17, which now defines the Th(17) immune response, is a critical cytokine expressed and required for stress granulopoiesis during microbial invasion. Dendritic cells (DC) can instigate this response by inducing IL-17 expression in CD4(+) T cells. Besides IL-17, microbial invasion also stimulates production of the DC growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF). The objective was the in vitro and in vivo investigation of IL-17 on DC proliferation and function in mice.


METHODS
Murine IL-17 (mIL-7) or murine GM-CSF (mGM-CSF), or both, was expressed in C57BL6 mice using adenoviral technology to assess hematopoietic and DC changes. The E-22 tymoma tumor cell line using a previously described vaccinia virus ovalbumin/LacZ murine tumor model was employed to study effects on tumor rejection.


RESULTS
The combination of mIL-17 and mGM-CSF increased peripheral neutrophila by 28-fold and splenic colonies by 11- and 14-fold over each individual factor in mice, respectively. The effect of mIL-17 by itself on murine DCs in vitro and in vivo was minimal; however, the combination greatly enhanced the stimulating effects of mGM-CSF, increasing the total numbers of CD14b/c(+) spleen DC by fourfold, as well as their function measured by enhanced endocytosis. Mixed lymphocyte reactions using mIL-17/mGM-CSF cultured DCs stimulator cells enhanced lymphocyte responses by twofold over mGM-CSF alone. Vaccination against LacZ in the C57BL6 E22 syngenic thymoma tumor model effectively delayed tumor growth in animals pretreated with the mIL-17/mGM-CSF combination prior to vaccination.


CONCLUSIONS
mIL-17 effectively synergizes with mGM-CSF in stimulating granulopoiesis and DC expansion, as well as in functional enhancement of DCs.
Liu
Bainan
B
Quantumimmunologics, Tampa, FL 33623-0727, USA.
Tan
Weihong
W
Barsoum
Adel
A
Gu
Xiaogang
X
Chen
Kong
K
Huang
Weitao
W
Ramsay
Alistair
A
Kolls
Jay K
JK
Schwarzenberger
Paul
P
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D039481:CD11b Antigen / Q000378:metabolism; D039521:CD11c Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D004705:Endocytosis / Q000187:drug effects; D005822:Genetic Vectors / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015395:Histocompatibility Antigens Class I / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000187:drug effects*; D009374:Neoplasms, Experimental / Q000473:pathology / Q000517:prevention & control; D009504:Neutrophils / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D039481:CD11b Antigen; D039521:CD11c Antigen; D015395:Histocompatibility Antigens Class I; D020381:Interleukin-17; D016178:Granulocyte-Macrophage Colony-Stimulating Factor