Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

Dhodapkar, Kavita M.; Banerjee, Devi; Connolly, John F.; Kukreja, Anjli; Matayeva, Elyana; Verı̀, Maria Concetta; Ravetch, Jeffrey V.; Steinman, Ralph M.; Dhodapkar, Madhav V.

doi:10.1084/jem.2006254508232007c

Cited by 3 publications

(3 citation statements)

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“…Interestingly, at the cytokine level, the absence of Fc effector function conferred by the N297Q mutation induced significantly higher levels of TNF-a, IL-12p70, and IFN-g in human DCs, which suggests that Fc-FcgR engagement on DCs may negatively regulate CD40-mediated activation. Human monocyte-derived DCs express predominantly FcgRIIA and FcgRIIB; moreover, FcgRIIBmediated DC suppression has been described before (Boruchov et al, 2005;Dhodapkar et al, 2007). FcgRIIB present on DCs (in cis or in trans) could potentially influence CD40 activation through the ITIM signaling motif (Pauls and Marshall, 2017).…”

Section: Ll Open Accessmentioning

confidence: 89%

Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity

Chan

Fisher

et al. 2020

Cancer Cell

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Section: Ll Open Accessmentioning

confidence: 89%

Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity

Chan

Fisher

et al. 2020

Cancer Cell

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“…The main mechanism of action in the passive ITP model is antibody-mediated platelet phagocytosis by macrophages ( 35 – 37 ). Functions of macrophages such as phagocytosis and antigen presentation are controlled by the balance between the levels of activating FcγRs (FcgRI, IIa, and III) and that of the inhibitory receptor, FcγRIIb ( 38 ). Liu and colleagues reported an increase in CD64 expression, as well in the CD32a/CD32b ratio, in circulating monocytes in ITP patients.…”

Section: Discussionmentioning

confidence: 99%

Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia

Xiang

Liu

et al. 2021

Front. Immunol.

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The immunoproteasome, a special isoform of the 20S proteasome, is expressed when the cells receive an inflammatory signal. Immunoproteasome inhibition proved efficacy in the treatment of autoimmune diseases. However, the role of the immunoproteasome in the pathogenesis of immune thrombocytopenia (ITP) remains unknown. We found that the expression of the immunoproteasome catalytic subunit, large multifunctional protease 2 (LMP2), was significantly upregulated in peripheral blood mononuclear cells of active ITP patients compared to those of healthy controls. No significant differences in LMP7 expression were observed between patients and controls. ML604440, an specific LMP2 inhibitor, had no significant impact on the platelet count of ITP mice, while ONX-0914 (an inhibitor of both LMP2 and LMP7) increased the number of platelets. In vitro assays revealed that ONX-0914 decreased the expression of FcγRI in ITP mice and decreased that of FcγRIII in ITP patients, inhibited the activation of CD4+ T cells, and affected the differentiation of Th1 cells in patients with ITP. These results suggest that the inhibition of immunoproteasome is a potential therapeutic approach for ITP patients.

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“…In addition, the recent finding that the interferon signature can be elicited in human monocytes in the absence of IFN-α by ligation of activating Fc receptors, together with blockade of inhibitory Fc receptors, suggests that there are multiple pathways for induction of inflammation by immune complexes (Ref. 180). Early clinical trials of anti-IFN antibodies are in process and should more definitively define the pathogenic role of this group of cytokines in SLE.…”

Section: Cytokines In Sle – Pleiotropic Activities May Complicate Trementioning

confidence: 99%

Targeting of the immune system in systemic lupus erythematosus

Ramanujam

Davidson

2008

Expert Rev. Mol. Med.

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Systemic lupus erythematosus (SLE) is a complex immune disorder in which loss of tolerance to nucleic acid antigens and other crossreactive antigens is associated with the development of pathogenic autoantibodies that damage target organs, including the skin, joints, brain and kidney. New drugs based on modulation of the immune system are currently being developed for the treatment of SLE. Many of these new therapies do not globally suppress the immune system but target specific activation pathways relevant to SLE pathogenesis. Immune modulation in SLE is complicated by differences in the immune defects between patients and at different disease stages. Since both deficiency and hyperactivity of the immune system can give rise to SLE, the ultimate goal for SLE therapy is to restore homeostasis without affecting protective immune responses to pathogens. Here we review recent immunological advances that have enhanced our understanding of SLE pathogenesis and discuss how they may lead to the development of new treatment regimens.

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Selective blockade of the inhibitory Fcγ receptor (FcγRIIB) in human dendritic cells and monocytes induces a type I interferon response program

Cited by 3 publications

References 0 publications

Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity

Isotype Switching Converts Anti-CD40 Antagonism to Agonism to Elicit Potent Antitumor Activity

Co-Inhibition of the Immunoproteasome Subunits LMP2 and LMP7 Ameliorates Immune Thrombocytopenia

Targeting of the immune system in systemic lupus erythematosus

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