Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients

Ohkuma, Koichi; Sasaki, Takeshi; Kamei, Satoshi; Okuda, Sachio; Nakano, Hiroyasu; Hamamoto, Takayoshi; Fujihara, Kazuo; Nakashima, Ichiro; Misu, Tatsuro; Itoyama, Yasuto

doi:10.1111/j.1365-2249.2007.03496.x

Cited by 16 publications

(7 citation statements)

References 46 publications

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“…33 In contrast, Ohkuma et al reported that the expression of CD86 remained high in IVIg-treated human DCs, 43 in agreement with our results obtained with murine BMDCs. The discrepancies between these results may be explained by differences in culture and other experimental conditions used to derive and treat DCs.…”

Section: Discussionsupporting

confidence: 92%

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Aubin

Lemieux

Bazin

2010

Blood

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Section: Discussionsupporting

confidence: 92%

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Aubin

Lemieux

Bazin

2010

Blood

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“…It has been reported that iTregs can be differentiated by co-culturing CD4+CD25− T cells with dendritic cells (DCs), which are antigen-presenting cells. 13) Therefore, we added IgG to this experimental system and investigated the effect of IgG on iTregs differentiation. imDCs were used in this experiment.…”

Section: Effect Of Igg On Itregs Differentiationmentioning

confidence: 99%

“…12) On the other hand, it has been reported that iTregs can be differentiated in vitro by activating progenitor cells CD4+CD25+Foxp3− cells with anti-CD3 antibody and culturing with the addition of interleukin (IL)-2 and transforming growth factor-β (TGF-β). 13) Using this experimental system, we attempted to clarify whether iTregs are involved in the immunomodulatory action of IVIg by investigating how IgG, which is a material of IVIg, exerts influence on the differentiation and function of iTregs. Our results showed that IgG enhanced iTregs differentiation from progenitor cells in a concentration-dependent manner, suppressing the proliferative response of T cells derived from the same individual depending on the expression of FoxP3.…”

mentioning

confidence: 99%

Immunoglobulin G Enhances Generation of Inducible T Regulatory Cells and Increases Their Regulatory Function

Okuda

Kamei

Sasaki

2018

Biological & Pharmaceutical Bulletin

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Intravenous immunoglobulin (IVIg) has been shown to be effective in the treatment of a variety of autoimmune diseases. To clarify the role of T regulatory cells (Tregs) in the immunoregulatory effect of IVIg, we focused on human inducible T regulatory cells (iTregs) and investigated the mechanism of action of IVIg. When immunoglobulin G (IgG) was added to a culture system that differentiates iTregs from anti-CD3 antibody activated CD4 CD25 T cells in the presence of syngeneic immature dendritic cells, interleukin (IL)-2 and transforming growth factor-β (TGF-β), the expression of forkhead box P3 (FoxP3), which is the master transcription factor for Tregs in CD4 CD25 T cells, increased in an IgG concentration-dependent manner. The expression of FoxP3 in iTregs in the 20 mg/mL IgG group was twice as high as that in the saline group. iTregs that highly expressed FoxP3 not only partially suppressed the polyclonal proliferative response of T cells derived from the same individual but also produced significantly more inhibitory cytokines IL-10 and TGF-β. The ability of IgG to enhance iTregs differentiation was also observed in the Fc fragment, but not in the F(ab′) 2 fragment. These results suggest the clinical regulation of immune responses by IVIg administration may contribute at least to enhancing the differentiation of iTregs and partial immunosuppressive functions.

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“…DCs play a crucial role as professional antigen presenting cells in balancing the immune response and tolerance. Investigations on the mode of action of IVIG have revealed that it inhibits the activation of both human and murine DCs and the production of inflammatory cytokines 19,23,27 The ability of IVIG to suppress DC activation also had impact on the DC-mediated T cell responses and the pathogenesis of autoimmune diseases 19,20,55,61,62 . The signaling pathway(s) that are implicated in the regulation of DC functions by IVIG is not well understood.…”

Section: Resultsmentioning

confidence: 99%

“…It is interesting to note that IVIG has been reported to suppress the inflammatory cytokines in DCs and reciprocally regulate Tregs and effector Th1/Th17 responses in vitro, in vivo in EAE model, and in treated autoimmune patients [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] . In view of reports on the central role of β-catenin/Wnt pathway in mediating these anti-inflammatory effects, we hypothesized that IVIG induces the activation of β-catenin/Wnt pathway to exert antiinflammatory effects.…”

mentioning

confidence: 99%

Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells

et al. 2020

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Therapeutic normal IgG intravenous immunoglobulin (IVIG) is a well-established first-line immunotherapy for many autoimmune and inflammatory diseases. Though several mechanisms have been proposed for the anti-inflammatory actions of IVIG, associated signaling pathways are not well studied. As β-catenin, the central component of the canonical Wnt pathway, plays an important role in imparting tolerogenic properties to dendritic cells (DCs) and in reducing inflammation, we explored whether IVIG induces the β-catenin pathway to exert anti-inflammatory effects. We show that IVIG in an IgG-sialylation independent manner activates β-catenin in human DCs along with upregulation of Wnt5a secretion. Mechanistically, β-catenin activation by IVIG requires intact IgG and LRP5/6 coreceptors, but FcγRIIA and Syk are not implicated. Despite induction of β-catenin, this pathway is dispensable for anti-inflammatory actions of IVIG in vitro and for mediating the protection against experimental autoimmune encephalomyelitis in vivo in mice, and reciprocal regulation of effector Th17/Th1 and regulatory T cells.

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Modulation of dendritic cell development by immunoglobulin G in control subjects and multiple sclerosis patients

Cited by 16 publications

References 46 publications

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Indirect inhibition of in vivo and in vitro T-cell responses by intravenous immunoglobulins due to impaired antigen presentation

Immunoglobulin G Enhances Generation of Inducible T Regulatory Cells and Increases Their Regulatory Function

Therapeutic normal IgG intravenous immunoglobulin activates Wnt-β-catenin pathway in dendritic cells

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