FcγRIIa cross-talk with TLRs, IL-1R, and IFNγR selectively modulates cytokine production in human myeloid cells

Vogelpoel, Lisa T.C.; Hansen, Ivo S.; Visser, Marijke W.; Nagelkerke, Sietse Q.; Kuijpers, Taco W.; Kapsenberg, Martien L.; Jong, Esther C. de; Dunnen, Jeroen den

doi:10.1016/j.imbio.2014.07.016

Cited by 52 publications

(81 citation statements)

References 45 publications

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“…We then showed that hypomethylation at gene promoters of TLR1, 2, 4, 6, 8, and 9 increases the expression of downstream genes. Vogelpoel et al reported that the cross-talk between FCGR2A and TLRs in human dendritic cells activated anti-bacterial immunity through the selective induction of TNFα and Th17-promoting cytokines response, which agrees with our previous findings regarding Th-17, TNFα, and FCGR2A in KD [17, 34]. The present study is the first to demonstrate that epigenetics of DNA methylation on TLRs may influence downstream gene expression in KD.…”

Section: Discussionsupporting

confidence: 92%

Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

Huang

et al. 2017

Oncotarget

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Kawasaki disease (KD) is an acute febrile systemic vasculitis that occurs in children and is characterized by elevated levels of proinflammatory cytokines. Toll-like receptors (TLRs) serve as the sensor arm of the innate immune system and induce proinflammatory cytokine expressions.We recruited a total of 18 paired KD patients, before intravenous immunoglobulin (IVIG) and at least 3 weeks after IVIG treatment, 18 healthy controls, and 18 febrile controls. For TLR genes and their cytosine-phosphate-guanine (CpG) markers, we used Affymetrix GeneChip® Human Transcriptome Array 2.0 and Illumina HumanMethylation450 BeadChip to evaluate gene expression levels and methylation patterns, respectively.KD patients demonstrated a significantly differential expression of TLR mRNA levels compared to both the healthy and febrile controls, with only TLR 3 and 7 not differing between the KD patients and the controls. After patients underwent IVIG treatment, the TLR mRNA levels, except for TLR3, decreased significantly in KD patients. In contrast, the methylation status of the CpG sites of TLR1, 2, 4, 6, 8, and 9 demonstrated an opposite tendency between the two stages of both the KD samples and the controls.TLRs, particularly TLR1, 2, 4, 6, 8, and 9, may stimulate the immunopathogenesis of KD. These results are among the first to use TLRs to prove that a bacterial inflammatory response may trigger KD.

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Section: Discussionsupporting

confidence: 92%

Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

Huang

et al. 2017

Oncotarget

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“…In contrast, only the endosomal expressed TLR3 was not able to synergize with FcγRs on DCs to produce IL‐1β and IL‐23 . Monocytes and macrophages, which express FcγRI, FcγRIIa, and FcγRIIIa induced increased levels of TNFα and IL‐1β after co‐ligation with TLR2 or TLR4, compared to single stimulation with either complexed IgG or TLR ligands . Blocking FcγRIIa on these cell types strongly affected synergistic release of TNFα.…”

Section: Tlrs and Fcrs Acting Together To Eradicate Infectionsmentioning

confidence: 94%

Cross‐talk between pathogen recognizing Toll‐like receptors and immunoglobulin Fc receptors in immunity

Egmond

Vidarsson

Bakema

2015

Immunological Reviews

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The individual role of pathogen-binding Toll-like receptors (TLRs) and antibody-binding Fc receptors (FcRs) during pathogenic infections has been studied extensively. However, combined activation of these different receptor classes has received little attention, even though they are triggered simultaneously when immune cells bind antibody-opsonized pathogens. In the last few years, it has become evident that joined activation of TLRs and FcRs substantially tailors inflammatory immune responses, which is an efficient and controlled mechanism of the host to act upon invading pathogens. In this review, we discuss the mechanisms of cross-talk between different TLRs and FcRs and the resulting inflammatory immune responses. Furthermore, we propose how chronic activation via this cross-talk might be detrimental in inflammatory (auto) immune diseases. We conclude with the potential exploitation of the interplay between TLRs and FcRs for monoclonal antibody therapy to target tumors. Future interests in this field of research include establishing a more detailed and mechanistic understanding of the mode of action of TLR and FcR cross-talk and exploration of its physiological importance in health and disease. This may furthermore open up novel therapeutic options for intervention in inflammatory diseases or cancer.

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“…The BCR/TLR two-signal mechanism explains the high prevalence of autoantibodies against nuclear proteins in autoimmune diseases like systemic lupus erythematosus (SLE) [96]. Furthermore, M2 macrophages produced pro-inflammatory cytokines in the presence of IgG-TLR ligands, increasing the pro-inflammatory cytokine secretion and the polarization towards Th17, which are critical in the pathology of RA [97, 98]. Th17 is also involved in bone destruction via osteoclastogenesis [99].…”

Section: Tlrs In Activation Of Auto-reactive B Cells and Th17 Cellsmentioning

confidence: 99%

The critical role of toll-like receptors — From microbial recognition to autoimmunity: A comprehensive review

Jiménez-Dalmaroni

Gerswhin

Adamopoulos

2016

Autoimmunity Reviews

226

168

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Toll-like receptors (TLRs) constitute an important mechanism in the activation of innate immune cells including monocytes, macrophages and dendritic cells. Macrophage activation by TLRs is pivotal in the initiation of the rapid expression of pro-inflammatory cytokines TNF, IL-1β and IL-6 whilst promoting Th17 responses, all of which play critical roles in autoimmunity. Surprisingly, in inflammatory arthritis, activation of specific TLRs can not only induce but also inhibit cellular processes associated with bone destruction. The intercellular and intracellular orchestration of signals from different TLRs, their endogenous or microbial ligands and accessory molecules determines the activating or inhibitory responses. Herein, we review the TLR-mediated activation of innate immune cells in their activation and differentiation to osteoclasts and the capacity of these signals to contribute to bone destruction in arthritis. Detailed understanding of the opposing mechanisms of TLRs in the induction and suppression of cellular processes in arthritis may pave the way to develop novel therapies to treat autoimmunity.

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FcγRIIa cross-talk with TLRs, IL-1R, and IFNγR selectively modulates cytokine production in human myeloid cells

Cited by 52 publications

References 45 publications

Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

Identifying genetic hypomethylation and upregulation of toll-like receptors in Kawasaki disease

Cross‐talk between pathogen recognizing Toll‐like receptors and immunoglobulin Fc receptors in immunity

The critical role of toll-like receptors — From microbial recognition to autoimmunity: A comprehensive review

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