Tolerization of dendritic cells by HLA‐G

Ristich, Vladimir; Liang, Sai; Zhang, Wei; Wu, Juan; Horuzsko, Anatolij

doi:10.1002/eji.200425741

Cited by 288 publications

(267 citation statements)

References 28 publications

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“…ILT4 could contribute to the tolerogenic effect of ASPDCs following interaction with HLA-G as reported for IL-10-DCs (4). Although both treatments induce anergic T cells (74,75), generated cells are different because only IL-10 DCs induce bona fide Tr1s (4). ILT3 and CCL-22 are specifically downregulated in ASP-DCs but not DEX-DCs.…”

Section: Discussionmentioning

confidence: 99%

Identification of a New Phenotype of Tolerogenic Human Dendritic Cells Induced by Fungal Proteases from Aspergillus oryzae

Zimmer

Luce

Gaignier

et al. 2011

The Journal of Immunology

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We characterized a new pathway to induce tolerogenic dendritic cells (DCs) following treatment of human monocyte-derived DCs with proteases from the fungus Aspergillus oryzae (ASP). ASP-treated DCs (ASP-DCs) exhibit a CD80−CD83−CD86−Ig-like transcript (ILT)2−ILT3−ILT4+ phenotype, do not secrete cytokines or chemokines, and express tolerogenic markers such as glucocorticoid-induced leucine zipper, NO synthetase-2, retinaldehyde dehydrogenase-1 or retinaldehyde dehydrogenase-2. When cocultured with naive CD4+ T cells, ASP-DCs induce an anergic state that can be reversed by IL-2. Generated T cells mediate a suppressive activity in third-party experiments that is not mediated by soluble factors. A comparison between dexamethasone-treated DCs used as a reference for regulatory T cell-inducing DCs and ASP-DCs reveals two distinct phenotypes. In contrast to dexamethasone, ASP treatment induces glucocorticoid-induced leucine zipper independently of glucocorticoid receptor engagement and leads to NF-κB p65 degradation. Abrogation of protease activities in ASP using specific inhibitors reveals that aspartic acid-containing proteases are key inducers of regulatory genes, whereas serine, cysteine, and metalloproteases contribute to NF-κB p65 degradation. Collectively, those features correspond to a previously unreported anergizing phenotype for human DCs. Such regulatory mechanisms may allow fungi to downregulate host immune responses and provide clues for new approaches to treat proinflammatory disorders.

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Section: Discussionmentioning

confidence: 99%

Identification of a New Phenotype of Tolerogenic Human Dendritic Cells Induced by Fungal Proteases from Aspergillus oryzae

Zimmer

Luce

Gaignier

et al. 2011

The Journal of Immunology

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“…It is expressed in some types of cancers, transplantations, autoimmune diseases, inflammatory conditions and viral infections. HLA-G was found to inhibit functions of NK cells and CTLs (99), induce regulatory cells (100-102), inhibit allogenic responses (100, 101) and DC maturation (102), and up-regulate inhibitory receptor expression (103). HLA-G has been shown to transfer from APCs to T cells resulting in functional consequences.…”

Section: Suppressive Effect On Immune Responsesmentioning

confidence: 99%

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

et al. 2008

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“…Several HLA-G mediated escape mechanisms have been described. As summarized in Fig.1, they include i) inhibition of cytotoxic activity of CTL and NK cells [8,9], ii) inhibition of CD4 + T cell proliferation and cytokine release [10,11], iii) inhibition of cell cycle progression in human alloreactive T cells [12]; iv) generation of a new type of regulatory CD4 + or CD8 + T cells through transfer of membrane HLA-G from antigen presenting cells to activated T cells ("trogocytosis") [13]; v) induction of tolerogenic dendritic cells (DC) associated with inhibition of their differentiation [14], and vi) induction of a Th2-like cytokine profile at tumor site through stimulation of IL-3, IL-4 and IL-10 secretion [15].…”

Section: Introductionmentioning

confidence: 99%

Soluble HLA-G: Are they clinically relevant?

Pistoia¹,

Morandi²,

Wang³

et al. 2007

Seminars in Cancer Biology

162

182

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HLA-G is a non-classical HLA-class Ib molecule with multiple immunoregulatory properties. Its main function in physiological conditions is to abrogate maternal NK cell activity against foetal tissue and to establish immune tolerance at maternal-foetal interface. HLA-G is expressed not only as a membrane bound molecule on the surface of cells, but also as a soluble moiety in body fluids. The major isoforms of HLA-G present in serum are soluble HLA-G1 and HLA-G5 which are generated by shedding or proteolytic cleavage of the membrane bound isoform and by secretion of a soluble isoform, respectively.Here we review the data about soluble HLA-G (sHLA-G) serum levels in different pathological conditions, including immune-mediated disorders, transplantation, and malignancies. In particular, we focus on sHLA-G expression and function in human neuroblastoma, a pediatric tumor, with special emphasis on a novel potential immuno escape mechanism utilized by NB to instruct monocytes to produce and release sHLA-G. Finally, the potential clinical relevance of sHLA-G serum levels is discussed.

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Tolerization of dendritic cells by HLA‐G

Cited by 288 publications

References 28 publications

Identification of a New Phenotype of Tolerogenic Human Dendritic Cells Induced by Fungal Proteases from Aspergillus oryzae

Identification of a New Phenotype of Tolerogenic Human Dendritic Cells Induced by Fungal Proteases from Aspergillus oryzae

Intercellular Trogocytosis Plays an Important Role in Modulation of Immune Responses

Soluble HLA-G: Are they clinically relevant?

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