What kind of message does IL-12/IL-23 bring to macrophages and dendritic cells?

Bastos, Karina R. B.; Marinho, Cláudio Romero Farias; Barboza, Renato; Russo, Marco; Álvarez, José María; Lima, Maria Regina D'Império

doi:10.1016/j.micinf.2004.02.012

Cited by 71 publications

(52 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This is somehow intriguing, because IL-23 is known to stimulate DCs to secrete IL-12 12 which, in turn, induces the production of IFN-c (a cytokine known to up-regulate MHC class II and CD86 expression) or the expression of IFN-c mRNA. 13 In fact, in peritoneal macrophages, IL-12 is able to induce the expression of these molecules by a mechanism dependent in endogenous IFN-c. 3 Our findings lead us to conclude that IL-12 and IL-23 have an important role in the modulation of the DC activation profile. These cytokines, acting through IFN-cdependent and -independent pathways, may signal DCs, macrophages and lymphocytes in the same direction, culminating in the optimization of mechanisms responsible for eliminating micro-organisms from host tissues.…”

Section: Discussionmentioning

confidence: 61%

“…These cytokines, acting through IFN-cdependent and -independent pathways, may signal DCs, macrophages and lymphocytes in the same direction, culminating in the optimization of mechanisms responsible for eliminating micro-organisms from host tissues. 3 Determining the source of IFN-c during LPS-induced maturation would be an important step in understanding the molecular pathways responsible for NO release by DCs. However, experiments carried out in our laboratory failed to detect (by using intracellular staining) the production of IFN-c by DCs stimulated with LPS.…”

Section: Discussionmentioning

confidence: 99%

“…12 In the last few years, it has been reported that one of the major effects of IL-12 on these cells is the induction of interferon-c (IFN-c) production, 13 which involves Stat4 and T-bet transcriptional factors. 14,15 Because of this effect of IL-12, some of its autocrine activities on DCs seem to be mediated by endogenous IFN-c. 3 The direct effect of IL-23 on IFN-c production by DCs has not yet been evaluated, but IL-23 induces IL-12 secretion by DCs, 12 which might contribute to IFN-c production by these cells. Moreover, the referred study also shows that IL-23 promotes peptide presentation equally well for both CD8 -and CD8 + DC subsets, whereas IL-12 acts selectively on CD8 -DCs.…”

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

“…Several reports have described the ability of IL-12 to induce IFN-c secretion by DCs, 13 raising the possibility that some of the autocrine activities attributed to IL-12 might be mediated by endogenous IFN-c. 3 To address this issue, we analysed NO and TGF-b1 production by mDCs derived from the bone marrow of IFN-c -/-and IL-12/IL-23 -/-IFN-c -/-mice. As shown in Fig.…”

Section: Generation Of Dcs From the Bone Marrow Of Il-12/il-23 -/-Andmentioning

confidence: 99%

“…Evidence in this direction has been gathered from data showing that cytokines produced by DCs, particularly interleukin (IL)-12 and IL-23, can act in an autocrine manner and modulate the activation pattern of these cells. 3,4 IL-12 is an heterodimeric cytokine formed by two chains -p35 and p40 -encoded by genes located on different chromosomes. 5 For generation of the bioactive IL-12p70 molecule, both genes must be expressed in the same cell.…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin‐12/interleukin‐23‐deficient mice

et al. 2005

Self Cite

View full text Add to dashboard Cite

SummaryWe 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-b1 (TGF-b1) and producing low levels of nitric oxide (NO) in response to lipopolysaccharide (LPS) and interferon-c (IFN-c). 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-b1 and lower levels of NO than C57BL/6 mDCs. NO release was IFN-c-dependent, as evidenced by the poor response of IFN-c -/-and IL-12/IL-23 -/-IFN-c -/-mDCs. Nevertheless, IFN-c 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-b1 secretion by IL-12/IL-23 -/-mDCs could explain why exogenous IFN-c partially restored the NO production of IFN-c -/-mDCs, while IL-12/IL-23 -/-IFN-c -/-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-c and NO appear to mediate this antiproliferative effect because this effect was not observed in the presence of mDCs from IFN-c -/-or IL-12/IL-23 -/-IFN-c -/-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-c dependent.

show abstract

Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Section: M M U N O L O G Y O R I G I N a L A R T I C L Ementioning

confidence: 99%

Section: Generation Of Dcs From the Bone Marrow Of Il-12/il-23 -/-Andmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin‐12/interleukin‐23‐deficient mice

et al. 2005

Self Cite

View full text Add to dashboard Cite

show abstract

Interleukin 23 in Acute Inflammatory Demyelination of the Peripheral Nerve

Hu¹,

Dehmel²,

Pirhonen³

et al. 2006

Arch Neurol

View full text Add to dashboard Cite

Background: Interleukin (IL) 23, a newly identified heterodimeric proinflammatory cytokine and a novel IL-12 family member comprising the p40 subunit of IL-12 but a different p19 subunit, has been reported to preferentially act on memory T cells and play an important role during cellular immune responses. Recent evidence suggests that IL-23 rather than IL-12 is critically involved in the pathogenesis of various immune-mediated disorders. Objective: To determine the role of IL-23p19 during the course of acute immune-mediated demyelinating diseases of the peripheral nervous system. Design: The sequential RNA expression of IL-23p19 in sciatic nerves from rats with experimental autoimmune neuritis, an animal model of the human Guillain-Barré syndrome (GBS), was analyzed by semiquantitative reverse transcriptase-polymerase chain reaction. Expression and distribution patterns of IL-23p19 protein were studied in sural nerve biopsies and cerebrospinal fluid samples from 5 patients with classical Guillain-Barré syndrome and 5 controls with noninflammatory neuropathies using immunohistochemistry and immunoblotting, respectively. Results: We found IL-23p19 RNA to be up-regulated prior to the onset of first clinical symptoms with peak expression levels preceding maximum disease severity during experimental autoimmune neuritis. In patients, IL-23p19 protein was detectable in cerebrospinal fluid samples from patients with Guillain-Barré syndrome, and endoneurial macrophages were identified as the cellular source of IL-23p19 in sural nerve biopsies. Conclusion: Our present data indicate that IL-23 may play an important role during the early effector phase in immune-mediated demyelination of the peripheral nerve.

show abstract

Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicity

et al. 2007

View full text Add to dashboard Cite

Self proteins may become autoantigenic through structural modification. We studied malondialdehydation of recombinant rat (rr) myelin oligodendrocyte glycoprotein (MOG), an autoantigen in multiple sclerosis. Malondialdehyde (MDA) modification changed protein weight and charge, the location of these adducts being mapped by Fourier transform ion cyclotron resonance. Molecular modelling revealed significant differences in the MDA‐rrMOG three‐dimensional structure. DBA/1 mice immunised with MDA‐rrMOG developed greater proliferative responses and more severe experimental autoimmune encephalomyelitis than mice immunised with unmodified rrMOG. MDA‐rrMOG was taken up more effectively by antigen‐presenting cells (APC), at least partially through scavenger receptors. Exposure to MDA‐rrMOG led to increased expression of IL‐23, IL‐12 and IL‐12R, indicating a role not only for increased antigen uptake but also for activation of APC. We thus provide biochemical, structural, immunological and clinical data that suggest that the post‐translationally modified form of this myelin autoantigen is a more relevant form of the molecule.

show abstract

What kind of message does IL-12/IL-23 bring to macrophages and dendritic cells?

Cited by 71 publications

References 44 publications

Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin‐12/interleukin‐23‐deficient mice

Analysis of the activation profile of dendritic cells derived from the bone marrow of interleukin‐12/interleukin‐23‐deficient mice

Interleukin 23 in Acute Inflammatory Demyelination of the Peripheral Nerve

Malondialdehyde modification of myelin oligodendrocyte glycoprotein leads to increased immunogenicity and encephalitogenicity

Contact Info

Product

Resources

About