Induction of dendritic cell maturation by IL-18.
IL-18 is a pluripotent proinflammatory cytokine produced primarily by antigen presenting cells involved in numerous aspects of immune regulation most notably on lymphoid cells. The effect of IL-18 stimulation on cells in the myeloid compartment, however, has been poorly studied. Human monocytes did not respond to IL-18. However, the human myelomonocytic cell line KG-1 and monocyte-derived dendritic cells (generated by GM-CSF+IL-4) showed a marked increase in CD83, HLA-DR, and several costimulatory molecules upon stimulation with IL-18. Furthermore, IL-18 decreased pinocytosis of these cells and increased their ability to stimulate alloreactive T cell proliferation, all characteristics of mature dendritic cells. These results suggest that IL-18 is involved in the maturation of myeloid DCs, but not differentiation of monocytes into DCs. The finding that IL-18 is involved in the maturation of dendritic cells is both novel and unexpected and indicates another important role for IL-18 as a key regulator of immune responses.
Li
Jian
J
Department of Immunobiology, Centocor, Inc. 200 Great Valley Parkway, Malvern, PA 19355, USA. jli14@cntus.jnj.com
Mbow
M Lamine
ML
Sun
Li
L
Li
Li
L
Yang
Gaoyun
G
Griswold
Don E
DE
Schantz
Allen
A
Shealy
David J
DJ
Goletz
Theresa J
TJ
Wan
Jackson
J
Peritt
David
D
D002460:Cell Line; D003713:Dendritic Cells / Q000187:drug effects* / Q000502:physiology; D004705:Endocytosis / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020382:Interleukin-18 / Q000494:pharmacology*; D053727:Interleukin-18 Receptor alpha Subunit; D007959:Lymphocyte Culture Test, Mixed; D018123:Receptors, Interleukin / Q000235:genetics; D053724:Receptors, Interleukin-18; D015854:Up-Regulation
C508572:IL18R1 protein, human; D020382:Interleukin-18; D053727:Interleukin-18 Receptor alpha Subunit; D018123:Receptors, Interleukin; D053724:Receptors, Interleukin-18