Induction of T cells suppression by dendritic cells transfected with VSIG4 recombinant adenovirus

Xu, Shuxiong; Sun, Zhaolin; Li, Lian; Li, Jun; He, Jianmei; Song, Dalong; Shan, Gang; Hong, Liu; Wu, Xiongfei

doi:10.1016/j.imlet.2009.11.003

Cited by 28 publications

(27 citation statements)

References 24 publications

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“…First, we verified that a CRIg-Fc fusion protein could suppress the proliferation of NOD T cells when cultured in vitro , in a dose-dependent manner (Supplementary Fig. 7), as has been reported in other contexts for other mouse strains 19, 23, 24 . To determine whether CRIg expression by pancreas-resident MFs might have a causal relationship with MRI signal intensity and eventual diabetes development, we injected cohorts of female NOD mice with either CRIg-Fc or a control Fc fusion protein from 3–10 weeks of age, an interval that spans the initiation and establishment of insulitis.…”

Section: Resultssupporting

confidence: 76%

“…5a). Our attention was drawn in particular to a recently identified complement pathway component, CRIg, because it is expressed exclusively on tissue-resident MFs 18–22 , it has been reported to inhibit T cell activation, proliferation and cytokine production 19, 23, 24 , and Fc fusions can modulate autoimmune/inflammatory diseases 24–26 . Crig transcript levels in pancreatic CD45 + cells showed a strong negative correlation with T2 pre-MNP signals (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Of the set of transcripts enriched is the islet infiltrates of diabetes-nonprogressors, we were particularly intrigued by those encoding CRIg because this molecule is expressed exclusively by tissue-resident MFs 18–22 , can inhibit T cell activation, proliferation and cytokine production 19, 23, 24 , and derivative reagents modulate autoimmune/inflammatory diseases, notably experimental arthritis and uveitis 24–26 . Indeed, CRIg proved relevant in the current context: it marked a specific subset of MFs whose representation in the insulitic infiltrate showed a significant negative correlation with 10-week MRI values and most importantly, administration of a CRIg-Fc fusion protein both lowered the MRI values and inhibited development of T1D.…”

Section: Discussionmentioning

confidence: 99%

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Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging

et al. 2012

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All juvenile NOD mice exhibit insulitis, but there is substantial variation in their progression to diabetes. We demonstrate that a patient-validated magnetic-resonance-imaging (MRI) strategy to non-invasively visualize local effects of pancreatic-islet inflammation can predict diabetes onset in NOD mice. MRI signals acquired during a narrow early time-window allowed pre-sorting into disease-progressors and -nonprogressors and an estimate of time-to-diabetes. We exploited this capability to identify novel elements correlated with disease protection, including CRIg (complement receptor of the immunoglobulin superfamily), which marked a subset of macrophages associated with diabetes resistance. Administration of CRIg-Fc depressed MRI signals and diabetes incidence. In addition to identifying regulators of disease progression, this study shows that diabetes is set at an early age in NOD mice.

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Section: Resultssupporting

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging

et al. 2012

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“…For example, human dendritic cells transfected with CRIg inhibited the proliferation of CD4 ϩ and CD8 ϩ T cells and decreased the expression of activation markers (CD25 and CD69) and secretion of proinflammatory cytokines by these cells. 31 In vivo, the number of intrahepatic CRIg ϩ macrophages in untreated chronic hepatitis B patients was found to be inversely correlated with serum alanine aminotransferase, a marker of liver inflammation, but was positively correlated with plasma hepatitis B viral load, 28 consistent with CRIg having an anti-T-cell function. On the other hand, others have shown that cross-linking of CRIg (or Z39Ig) on human monocytic THP-1 cells causes nuclear translocation of nuclear factor-B and increases expression of matrix metallopeptidase-9 and secretion of IL-8, and that PMA treatment of the human myeloid leukemia cell line TF-1A resulted in increased expression of CRIg.…”

Section: Discussionmentioning

confidence: 99%

Regulation of CRIg Expression and Phagocytosis in Human Macrophages by Arachidonate, Dexamethasone, and Cytokines

Gorgani

Thathaisong

Mukaro

et al. 2011

The American Journal of Pathology

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Although the importance of the macrophage complement receptor immunoglobulin (CRIg) in the phagocytosis of complement opsonized bacteria and in inflammation has been established, the regulation of CRIg expression remains undefined. Because cellular activation during inflammation leads to the release of arachidonate, a stimulator of leukocyte function, we sought to determine whether arachidonate regulates CRIg expression. Adding arachidonate to maturing human macrophages and to prematured CRIg ؉ macrophages caused a significant decrease in the expression of cell-surface CRIg and CRIg mRNA. This effect was independent of the metabolism of arachidonate via the cyclooxygenase and lipoxygenase pathways, because it was not inhibited by the nonsteroidal anti-inflammatory drugs indomethacin and nordihydroguaiaretic acid. Studies with specific pharmacological inhibitors of arachidonate-mediated signaling pathways showed that protein kinase C was involved. Administration of dexamethasone to macrophages caused an increase in CRIg expression. Studies with proinflammatory and immunosuppressive cytokines showed that IL-10 increased, but interferon-␥, IL-4, and transforming growth factor-␤1 decreased CRIg expression on macrophages. This down-and upregulation of CRIg expression was reflected in a decrease and increase, respectively, in the phagocytosis of complement opsonized Candida albicans. These data suggest that a unique inflammatory mediator network regulates CRIg expression and point to a mechanism by which arachidonate and dexamethasone have reciprocal effects on inflammation.

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“…Another interesting and potential M2 marker is VSIG4, a B7 family-related molecule previously shown to be expressed in resting Mf but not in LPS-stimulated Mf (43). This protein was observed to mediate inhibition of T cell proliferation by Mf and dendritic cells (43,74), suggesting a role in keeping tissue homeostasis. Although the exact functions of these genes in pregnancy are not known and their expression needs to be confirmed at the protein level, they support an M2 polarization pattern of decidual Mf mainly induced by M-CSF and IL-10.…”

Section: Discussionmentioning

confidence: 99%

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

Svensson

Jenmalm

Matussek

et al. 2011

The Journal of Immunology

315

314

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During pregnancy, the maternal immune system is challenged by the presence of the fetus, which must be tolerated despite being semiallogeneic. Uterine mucosal (or decidual) macrophages (Mϕ), one of the major leukocyte populations at the fetal–maternal interface, have been implicated in fetal tolerance, but information regarding their regulation is scarce. In this study, we investigated the role of several factors potentially involved in the differentiation and polarization of decidual Mϕ with an in vitro Mϕ differentiation model. By using flow cytometry, we showed that M-CSF and IL-10 were potent inducers of M2 (immunoregulatory) Mϕ markers expressed on human decidual Mϕ (CD14, CD163, CD206, CD209). In contrast, proinflammatory stimuli, and unexpectedly also the Th2-associated IL-4 and IL-13, induced different patterns of expression, indicating that a Th2-dominated environment is not required for decidual Mϕ polarization. M-CSF/IL-10–stimulated and decidual Mϕ also showed similar cytokine secretion patterns, with production of IL-10 as well as IL-6, TNF, and CCL4. Conversely, the proinflammatory, LPS/IFN-γ–stimulated Mϕ produced significantly higher levels of TNF and no IL-10. We also used a gene array with 420 Mϕ-related genes, of which 100 were previously reported to be regulated in a global gene expression profiling of decidual Mϕ, confirming that M-CSF/IL-10–induced Mϕ are closely related to decidual Mϕ. Taken together, our results consistently point to a central role for M-CSF and in particular IL-10 in the shaping of decidual Mϕ with regulatory properties. These cytokines may therefore play an important role in supporting the homeostatic and tolerant immune milieu required for a successful pregnancy.

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Induction of T cells suppression by dendritic cells transfected with VSIG4 recombinant adenovirus

Cited by 28 publications

References 24 publications

Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging

Early window of diabetes determinism in NOD mice, dependent on the complement receptor CRIg, identified by noninvasive imaging

Regulation of CRIg Expression and Phagocytosis in Human Macrophages by Arachidonate, Dexamethasone, and Cytokines

Macrophages at the Fetal–Maternal Interface Express Markers of Alternative Activation and Are Induced by M-CSF and IL-10

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