Analysis of the Activation Profile of Dendritic Cells Derived from the Bone Marrow of Interleukin-12/interleukin-23-deficient Mice

Overview

Journal Immunology

Specialty Allergy & Immunology

Date 2005 Apr 5

PMID 15804287

Citations 8

Authors

Karina R B Bastos

Luciana de Deus Vieira de Moraes

Claudia A Zago

Claudio R F Marinho

Momtchilo Russo

Jose M M Alvarez

Maria R DImperio Lima

Affiliations

Soon will be listed here.

Abstract

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-beta1 (TGF-beta1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon-gamma (IFN-gamma). 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 approximately 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-beta1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN-gamma-dependent, as evidenced by the poor response of IFN-gamma-/- and IL-12/IL-23-/-IFN-gamma-/- mDCs. Nevertheless, IFN-gamma 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-beta1 secretion by IL-12/IL-23-/- mDCs could explain why exogenous IFN-gamma partially restored the NO production of IFN-gamma-/- mDCs, while IL-12/IL-23-/- IFN-gamma-/- 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-gamma and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN-gamma-/- or IL-12/IL-23-/- IFN-gamma-/- 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-gamma dependent.

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