Interleukin‐10 differentially regulates B7‐1 (CD80) and B7‐2 (CD86) expression on human peripheral blood dendritic cells

Buelens, Christel; Willems, Fabienne; Delvaux, Anne; Pierard, Géraldine; Delville, J. P.; Velu, Thierry; Goldman, Michel

doi:10.1002/eji.1830250940

Cited by 256 publications

(145 citation statements)

References 31 publications

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“…These results clearly indicate that mTORC1 positively regulates IL-10 expression in LP-DCs. Because IL-10 is known to suppress CD86 expression in DCs in vitro (16), it is likely that the increased expression of CD86 in LP-CD11c +…”

Section: Lp-cd11bmentioning

confidence: 99%

Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production

Ohtani

Hoshii

Fujii

et al. 2012

The Journal of Immunology

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The mammalian target of rapamycin (mTOR) controls cell growth and survival through two distinct complexes called mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). Although several reports have suggested the involvement of mTORC1 in development and function of dendritic cells (DCs), its physiological roles remain obscure. We therefore established mTORC1 signal-deficient mice lacking Raptor, an essential component of mTORC1 signal, specifically in DC lineage (referred to here as RaptorDC−/−). RaptorDC−/− mice exhibited cell expansion in specific subsets of DCs such as splenic CD8+ DCs and intestinal CD11c+CD11b+ DCs. We also found that impaired mTORC1 signal resulted in the suppression of IL-10 production along with enhanced CD86 expression in intestinal CD11c+CD11b+ DCs and that RaptorDC−/− mice were highly susceptible to dextran sodium sulfate-induced colitis. Our results uncover mTORC1-mediated anti-inflammatory programs in intestinal CD11c+CD11b+ DCs to limit the intestinal inflammation.

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Section: Lp-cd11bmentioning

confidence: 99%

Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production

Ohtani

Hoshii

Fujii

et al. 2012

The Journal of Immunology

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“…Therefore, DCs are believed to be largely plastic in function, and the expression of costimulatory markers and cytokines/molecules is likely to be more important for characterizing functional DC subsets. [78][79][80][81][82][83][84][85][86] Tolerogenic/regulatory DCs (DCregs), which may cause T-cell tolerance by different mechanisms, including T-cell depletion (apoptosis), T-cell hyporesponsiveness (anergy) and Treg induction, may be involved in the inhibition of allergic Th2 responses (Figure 1). Some CD8a 1 DCs express higher levels of Fas ligand (FasL) and are able to cause T-cell apoptosis.…”

Section: T-cell Responses and DC Functionmentioning

confidence: 99%

Role of dendritic cells: a step forward for the hygiene hypothesis

Yang

Gao

2010

Cell Mol Immunol

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The hygiene hypothesis was proposed more than two decades ago, but its mechanism remains unclear. This review focuses on recent advances in the field, especially on the role played by dendritic cells (DCs) and their modulating effects on various infections and allergic diseases, including allergic asthma. DCs isolated from mice long after the resolution of an infection were reported to have a significant modulating effect on allergen-specific Th2 responses in both in vitro and in vivo systems. These DCs showed DC1-like and/or tolerogenic DC capacity, which allowed for the inhibition of allergic responses by immune deviation (enhancing Th1 response) and immune regulation (through regulatory T-cell and Th2 hyporesponsiveness) mechanisms. These findings represented a significant advance in the elucidation of the mechanisms underlying the hygiene hypothesis. Further investigation on the mechanisms by which DCs are 'educated' by infectious agents and the influence of the type, time, and extent of infections on this 'education' process will help us understand immune regulation in disease settings and in the rational design of preventive/therapeutic approaches to allergy/asthma and infections.

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“…IL-10 is secreted by different tumors and may inhibit DC differentiation and function as well. 34,57 Wei and Jonakait 58 reported that IL-10 suppressed expression of CD40 molecules on cultured rat microglia. In addition, Tan et al 59 demonstrated that ligation of CD40 on cultured microglia cells by CD40L resulted in microglial activation, as measured by TNF-␣ production.…”

Section: Flt3l and Cd40l Administration In Mc38-bearing Mice Protectementioning

confidence: 99%

Inhibition of CD40 expression and CD40‐mediated dendritic cell function by tumor‐derived IL‐10

Shurin

Yurkovetsky

Tourkova

et al. 2002

Intl Journal of Cancer

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As CD40 plays a key role in both antitumor immunity and DC maturation, we have studied the regulation of its expression during DC hematopoiesis (dendropoiesis) in vitro and in vivo in the tumor microenvironment. Using MC38 colon adenocarcinoma tumor models, we have demonstrated that DCs generated in vitro from bone marrow precursors obtained from tumor-bearers have significantly lower expression of CD40 molecules compared to DCs generated from tumor-free mice. Furthermore, CD40 expression on DCs isolated from the spleens of tumor-bearing mice was also significantly reduced, suggesting that tumor-derived factors inhibit CD40 expression on DCs during dendropoiesis both in vitro and in vivo. Interestingly, CD40 ligation on DCs generated from tumor-bearers did not result in inducible expression of IL-12 protein or IL-12 p40 mRNA. However, Staphylococcus aureus-induced IL-12 production by DCs was not altered in tumor-bearers, confirming that inhibition of IL-12 production by DCs generated in vitro from tumor-bearing mice was due to reduced expression of CD40 on DCs. We have also shown that MC38 tumor cells produce IL-10 and that exogenous IL-10 causes downregulation of CD40 expression on DCs. Key words: dendropoiesis; dendritic cell; immunosuppression; IL-10; CD40Escape from immune surveillance is a fundamental feature of tumors, which contributes to their uncontrolled growth, leading to death of the host. 1-3 The escape of malignant cells from immune recognition results from a defective function of cells of the immune system, including DCs, which play a key role in induction of specific immune responses. 4,5 Impairment of DC numbers and activity in cancer results in deficient expansion of specific CTLs and failure to eliminate tumor cells. 6 For example, alteration in the density and distribution of epidermal DCs in the peritumoral infiltrate of malignant melanoma may be responsible for determining the degree of T-cell activation. 7 Several studies have reported tumor-induced inhibition of DC function or differentiation. For instance, human DCs obtained from progressing chemotherapynonresponsive melanomas showed marked depression of CD86 expression and induction of anergy of syngeneic CD4 ϩ T cells. 8 Interestingly, this anergy could be overcome by showed that the ability of DCs isolated from breast cancer patients to stimulate allogeneic T lymphocytes was profoundly suppressed. Similar data were reported for human basal cell carcinoma DCs, which were deficient in CD80 and CD86 expression as well as in their ability to stimulate T-lymphocyte proliferation. 10 We demonstrated previously that tumor-derived factors not only cause premature apoptosis of DCs 11-15 but also significantly suppress DC generation and maturation in both murine and human cultures. 6,16 -19 Together, these data suggest that tumor-induced immune dysfunction is a generalized phenomenon and that determination of the mechanisms of DC dysfunction and protection of immune cells from tumor-induced disability is a crucial aspect of modern immunother...

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Interleukin‐10 differentially regulates B7‐1 (CD80) and B7‐2 (CD86) expression on human peripheral blood dendritic cells

Cited by 256 publications

References 31 publications

Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production

Cutting Edge: mTORC1 in Intestinal CD11c+CD11b+ Dendritic Cells Regulates Intestinal Homeostasis by Promoting IL-10 Production

Role of dendritic cells: a step forward for the hygiene hypothesis

Inhibition of CD40 expression and CD40‐mediated dendritic cell function by tumor‐derived IL‐10

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