Induction of PD-L1 on monocytes: A new mechanism by which IVIg inhibits mixed lymphocyte reactions

Padet, Lauriane; Loubaki, Lionel; Bazin, Renée

doi:10.1016/j.imbio.2014.04.001

Cited by 4 publications

(7 citation statements)

References 57 publications

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“…We first observed, as previously reported , that addition of IVIg to MLRs strongly inhibited the reaction. As shown in Fig.…”

Section: Resultssupporting

confidence: 80%

“…We recently showed that IVIg induces phenotypic changes in monocytes, and we proposed that these modulations were involved in the inhibitory effect of IVIg in MLRs . These changes included a decrease in CD80 expression and an increase in PD‐L1 expression on monocytes in IVIg‐supplemented MLRs, as observed after 24 h of culture (Fig.…”

Section: Resultsmentioning

confidence: 75%

“…Our results reveal that IVIg significantly increases the expression of miR‐511 in resting monocytes (2.7‐fold) as also observed in IVIg‐supplemented MLR. This modulation correlates with a decreased expression of CD80 on resting monocytes from IVIg‐treated PBMC . The expression of miR‐142‐3p in resting monocytes is also increased (4.2‐fold), suggesting that the inhibition of IL‐6 secretion in MLR is caused by the IVIg‐mediated up‐regulation of miR‐142‐3p.…”

Section: Resultsmentioning

confidence: 84%

“…IVIg is currently used as desensitization therapy in highly HLA‐sensitized patients to reduce antibody‐mediated rejection and is effective in the treatment of allograft rejection and GvHD . Several studies have revealed that IVIg exerts its anti‐inflammatory effect by acting both on humoral (neutralization of anti‐HLA ; B‐cell apoptosis ; modification of autoantibody and alloantibody levels by anti‐idiotypic antibodies present in IVIg ) and cellular responses (inhibition of complement activity ; reduction of the expression of MHC and costimulatory molecules on APC ; inhibition of leukocyte recruitment through inhibition of selectin and integrin functions ). We therefore propose that the modulation of specific miRNA expression observed in the present study may represent a relevant mechanism in both AMR‐ and T‐cell‐mediated rejection.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, a significant effect of IVIg in the treatment of GvHD after allogeneic bone marrow transplantation has been reported . The inhibitory effect of IVIg was also observed in mixed lymphocyte reactions (MLRs) used as an in vitro model of AR and GvHD . In this study, we evaluated whether the inhibitory effect of IVIg in MLRs could be explained by modulations in the expression of miRNAs relevant for AR and/or GvHD regulation.…”

mentioning

confidence: 99%

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Use of IVIg to identify potential miRNA targets for allograft rejection and GvHD therapy

Padet

Loubaki

Bazin

2015

Clinical Transplantation

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Allograft rejection (AR) and graft-versus-host disease (GvHD) are serious complications following transplantation. Micro-RNAs (miRNAs) have recently been identified as key players in the regulation of these disorders. Because intravenous immunoglobulin (IVIg) has shown therapeutic potential for the prophylaxis and post-transplant reduction of AR and GvHD, we hypothesized that the effect of IVIg could result from the modulation of specific miRNA expression. To identify such miRNA, we performed mixed lymphocyte reactions (MLRs) as an in vitro model of AR and GvHD, with or without IVIg. We herein show that IVIg strongly inhibits the MLRs. This inhibition is associated with a modulation in the expression of miRNAs implicated in the regulation of pro-inflammatory cytokine (IL-2, IL-6, IFN-γ) and costimulatory molecule (CD80) expression. We propose that these identified miRNAs could represent potential therapeutic targets for the prevention and therapy of AR and GvHD.

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“…We first observed, as previously reported , that addition of IVIg to MLRs strongly inhibited the reaction. As shown in Fig.…”

Section: Resultssupporting

confidence: 80%

Section: Resultsmentioning

confidence: 75%

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Use of IVIg to identify potential miRNA targets for allograft rejection and GvHD therapy

Padet

Loubaki

Bazin

2015

Clinical Transplantation

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Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

Colado

Elías

Martínez

et al. 2021

Sci Rep

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Hypogammaglobulinemia is the most frequently observed immune defect in chronic lymphocytic leukemia (CLL). Although CLL patients usually have low serum levels of all isotypes (IgG, IgM and IgA), standard immunoglobulin (Ig) preparations for replacement therapy administrated to these patients contain more than 95% of IgG. Pentaglobin is an Ig preparation of intravenous application (IVIg) enriched with IgM and IgA (IVIgGMA), with the potential benefit to restore the Ig levels of all isotypes. Because IVIg preparations at high doses have well-documented anti-inflammatory and immunomodulatory effects, we aimed to evaluate the capacity of Pentaglobin and a standard IVIg preparation to affect leukemic and T cells from CLL patients. In contrast to standard IVIg, we found that IVIgGMA did not modify T cell activation and had a lower inhibitory effect on T cell proliferation. Regarding the activation of leukemic B cells through BCR, it was similarly reduced by both IVIgGMA and IVIgG. None of these IVIg preparations modified spontaneous apoptosis of T or leukemic B cells. However, the addition of IVIgGMA on in vitro cultures decreased the apoptosis of T cells induced by the BCL-2 inhibitor, venetoclax. Importantly, IVIgGMA did not impair venetoclax-induced apoptosis of leukemic B cells. Overall, our results add new data on the effects of different preparations of IVIg in CLL, and show that the IgM/IgA enriched preparation not only affects relevant mechanisms involved in CLL pathogenesis but also has a particular profile of immunomodulatory effects on T cells that deserves further investigation.

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Heme oxygenase-1 is dispensable for the anti-inflammatory activity of intravenous immunoglobulin

Galeotti

Hegde

Das

et al. 2016

Sci Rep

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Intravenous immunoglobulin G (IVIG) is used in the therapy of various autoimmune and inflammatory conditions. The mechanisms by which IVIG exerts anti-inflammatory effects are not completely understood. IVIG interacts with numerous components of the immune system including dendritic cells, macrophages, T and B cells and modulate their functions. Recent studies have reported that heme oxygenase-1 (HO-1) pathway plays an important role in the regulation of inflammatory response in several pathologies. Several therapeutic agents exert anti-inflammatory effects via induction of HO-1. Therefore, we aimed at exploring if anti-inflammatory effects of IVIG are mediated via HO-1 pathway. Confirming the previous reports, we report that IVIG exerts anti-inflammatory effects on innate cells as shown by the inhibitory effects on IL-6 and nitric oxide production and confers protection in experimental autoimmune encephalomyelitis (EAE) model. However, these effects were not associated with an induction of HO-1 either in innate cells such as monocytes, dendritic cells and macrophages or in the kidneys and liver of IVIG-treated EAE mice. Also, inhibition of endogenous HO-1 did not modify anti-inflammatory effects of IVIG. These results thus indicate that IVIG exerts anti-inflammatory effects independent of HO-1 pathway.

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Induction of PD-L1 on monocytes: A new mechanism by which IVIg inhibits mixed lymphocyte reactions

Cited by 4 publications

References 57 publications

Use of IVIg to identify potential miRNA targets for allograft rejection and GvHD therapy

Use of IVIg to identify potential miRNA targets for allograft rejection and GvHD therapy

Immunomodulatory effects of different intravenous immunoglobulin preparations in chronic lymphocytic leukemia

Heme oxygenase-1 is dispensable for the anti-inflammatory activity of intravenous immunoglobulin

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