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Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin‐12/interleukin‐23‐deficient mice
Author(s) -
Bastos Karina R. B.,
De Deus Vieira de Moraes Luciana,
Zago Cláudia A.,
Marinho Cláudio R. F.,
Russo Momtchilo,
Alvarez José M. M.,
D'Império Lima Maria R.
Publication year - 2005
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/j.1365-2567.2005.02118.x
Subject(s) - interleukin , immunology , interleukin 4 , lipopolysaccharide , interleukin 12 , interleukin 15 , interleukin 10 , interferon , bone marrow , chemistry , biology , cytokine , cytotoxic t cell , in vitro , biochemistry
Summary We have previously shown that macrophages from interleukin (IL)‐12p40 gene knockout (IL‐12/IL‐23 –/– ) mice have a bias towards the M2 activation profile, spontaneously secreting large quantities of transforming growth factor‐β1 (TGF‐β1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon‐γ (IFN‐γ). To verify whether the activation profile of dendritic cells (DCs) is also influenced by the absence of IL‐12/IL‐23, bone marrow‐derived DCs from IL‐12/IL‐23 –/– and C57BL/6 mice were evaluated. At first we noticed that ≈ 50% of the C57BL/6 DCs were dead after LPS‐induced maturation, whereas the mortality of IL‐12/IL‐23 –/– DCs was < 10%, a protective effect that diminished when recombinant IL‐12 (rIL‐12) was added during maturation. Similarly to macrophages, mature IL‐12/IL‐23 –/– DCs (mDCs) produced higher levels of TGF‐β1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN‐γ‐dependent, as evidenced by the poor response of IFN‐γ –/– and IL‐12/IL‐23 –/– IFN‐γ –/– mDCs. Nevertheless, IFN‐γ deficiency was not the sole reason for the weak NO response observed in the absence of IL‐12/IL‐23. The high level of TGF‐β1 secretion by IL‐12/IL‐23 –/– mDCs could explain why exogenous IFN‐γ partially restored the NO production of IFN‐γ –/– mDCs, while IL‐12/IL‐23 –/– IFN‐γ –/– mDCs remained unresponsive. We also showed that CD4 + T‐cell proliferation was inhibited by C57BL/6 mDCs, but not by IL‐12/IL‐23 –/– mDCs. IFN‐γ and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN‐γ –/– or IL‐12/IL‐23 –/– IFN‐γ –/– mice and it was attenuated by aminoguanidine. We conclude that the presence of IL‐12/IL‐23 during LPS‐induced maturation influences the activation profile of DCs by a mechanism that is, only in part, IFN‐γ dependent.