First Author | Mayuzumi N | Year | 2009 |
Journal | Eur J Immunol | Volume | 39 |
Issue | 12 | Pages | 3331-42 |
PubMed ID | 19750479 | Mgi Jnum | J:155498 |
Mgi Id | MGI:4414615 | Doi | 10.1002/eji.200939472 |
Citation | Mayuzumi N, et al. (2009) IL-33 promotes DC development in BM culture by triggering GM-CSF production. Eur J Immunol 39(12):3331-42 |
abstractText | Short-term DC cultures generated with GM-CSF and other cytokines have markedly improved our ability to study the immunobiology of DC. Here, we tested 65 cytokines individually for their potential to promote the generation of CD11c+ cells in a murine BM culture system. In addition to several cytokines known to promote DC survival and/or growth, IL-33 was found to augment DC development time- and dose-dependently. Although the resulting CD11c+ cells generated in the presence of IL-33 exhibited a typical dendritic morphology, they expressed MHC class II molecules only at modest levels, showed negligible responses to TLR ligands, produced no detectable IL-12 p70, displayed PD-L1 and PD-L2 on the surface, and failed to activate immunologically naive T cells efficiently. IL-33-induced expansion of CD11c+ cells was completely blocked by anti-GM-CSF mAb, and GM-CSF mRNA and protein expression in BM culture was markedly elevated by added IL-33, indicating that IL-33 promotes in vitro DC generation indirectly by a GM-CSF-dependent manner. With regard to the cellular source, IL-33-dependent GM-CSF production was observed exclusively within the CD45+/FcepsilonRI+ BM population. Not only do our results reinforce the notion that GM-CSF serves as a primary DC growth factor, but they also reveal a previously unrecognized mechanism supporting DC development. |