title: Identification of a rat bone marrow-derived dendritic cell population which secretes both IL-10 and IL-12: evidence against a reciprocal relationship between IL-10 and IL-12 secretion.
abstract: The qualitative nature of immune responses induced by dendritic cells (DCs) is influenced by the balance of pro-inflammatory (e.g. IL-12) and anti-inflammatory (e.g. IL-10) cytokines that they secrete. Evidence to date suggests that IL-12 and IL-10 secretion is reciprocally regulated and that IL-10 inhibits IL-12 secretion. This study identifies a population of resting, immature rat bone marrow-derived DCs (BMDCs) which secretes IL-10, the IL-12(p70) heterodimer and the free IL-12(p40) subunit, the latter in vast excess of IL-12(p70). Counter-intuitively, activation with LPS induces the secretion of high and equivalent levels of IL-10 and IL-12(p40), but only quantitatively small increases in IL-12(p70). Neutralization of IL-10 increased the secretion of IL-12(p40) by resting BMDCs, but decreased IL-12(p40) secretion by LPS-activated BMDCs. Pre-incubation of resting BMDCs for 24h with neutralizing antibody to IL-10 reduced the subsequent secretion of IL-10 in allogeneic cultures of Lewis CD3(+) T cells with resting and LPS-activated Wistar BMDCs, and enhanced IL-12(p40) secretion in allogeneic cultures with LPS-activated BMDCs. IL-10 neutralization had no effect on the levels of IL-12(p70), IFN-gamma or IL-4 in allogeneic cultures. In summary, this study has identified a population of rat BMDCs that secretes low levels of bioactive IL-12(p70), but high levels of IL-10 and IL-12(p40). These findings argue against the concept that there is a reciprocal relationship between IL-10 and IL-12 secretion. They might also have implications for understanding the role of DCs in post-activation qualitative skewing of immune responses.
authors.affiliation: Immunobiology Research Unit, Division of Clinical Sciences (North), Clinical Sciences Centre (University of Sheffield), Northern General Hospital, Herries Road, Sheffield S5 7AU, UK.
authors.forename: Munitta
authors.initials: M
authors.lastname: Muthana
authors.forename: Barbara
authors.initials: B
authors.lastname: Fairburn
authors.forename: Shabana
authors.initials: S
authors.lastname: Mirza
authors.forename: Laura K
authors.initials: LK
authors.lastname: Slack
authors.forename: Kay
authors.initials: K
authors.lastname: Hopkinson
authors.forename: Alan G
authors.initials: AG
authors.lastname: Pockley
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000378:metabolism; D017252:CD3 Complex / Q000032:analysis; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism*; D018664:Interleukin-12 / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40; D007519:Isoantigens / Q000276:immunology / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D009500:Neutralization Tests; D021122:Protein Subunits / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D016207:Cytokines; D053762:Interleukin-12 Subunit p40; D007519:Isoantigens; D008070:Lipopolysaccharides; D021122:Protein Subunits; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma