Soluble CD83 inhibits human monocyte differentiation into dendritic cells in vitro

Lin, Hongyu; Liang, Shuang; Zhong, Zhenyu; Wen, Jiexia; Li, Wenyan; Wang, Liyue; Xu, Jian; Zhong, Fei; Li, Xiujin

doi:10.1016/j.cellimm.2014.08.003

Cited by 19 publications

(16 citation statements)

References 30 publications

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“…sCD83 is a potent inhibitor of anti-CD3-induced proliferation of T cells and production of IL-2 and IFN-␥ by PBMCs, but the molecular mechanism by which CD83 suppresses the immune system is not understood (52)(53)(54). Virus-mediated suppression of CD83 expression reduces the stimulatory capacity of human DCs (55).…”

Section: Discussionmentioning

confidence: 99%

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The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Chen

Zhang

Bai

et al. 2017

J Virol

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Porcine reproductive and respiratory syndrome, caused by porcine reproductive and respiratory syndrome virus (PRRSV), is a panzootic disease that is one of the most economically costly diseases to the swine industry. A key aspect of PRRSV virulence is that the virus suppresses the innate immune response and induces persistent infection, although the underlying mechanisms are not well understood. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and is associated with DC activation and immunosuppression of T cell proliferation when expressed as soluble CD83 (sCD83). In this study, we show that PRRSV infection strongly stimulates CD83 expression in porcine monocyte-derived DCs (MoDCs) and that the nucleocapsid (N) protein and nonstructural protein 10 (nsp10) of PRRSV enhance CD83 promoter activity via the NF-κB and Sp1 signaling pathways. R43A and K44A amino acid substitution mutants of the N protein suppress the N protein-mediated increase of CD83 promoter activity. Similarly, P192-5A and G214-3A mutants of nsp10 (with 5 and 3 alanine substitutions beginning at residues P192 and G214, respectively) abolish the nsp10-mediated induction of the CD83 promoter. Using reverse genetics, four mutant viruses (rR43A, rK44A, rP192-5A, and rG214-3A) and four revertants [rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R)] were generated. Decreased induction of CD83 in MoDCs was observed after infection by mutants rR43A, rK44A, rP192-5A, and rG214-3A, in contrast to the results obtained using rR43A(R), rK44A(R), rP192-5A(R), and rG214-3A(R). These findings suggest that PRRSV N and nsp10 play important roles in modulating CD83 signaling and shed light on the mechanism by which PRRSV modulates host immunity. Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically costly pathogens affecting the swine industry. It is unclear how PRRSV inhibits the host's immune response and induces persistent infection. The dendritic cell (DC) marker CD83 belongs to the immunoglobulin superfamily and has previously been associated with DC activation and immunosuppression of T cell proliferation and differentiation when expressed as soluble CD83 (sCD83). In this study, we found that PRRSV infection induces sCD83 expression in porcine MoDCs via the NF-κB and Sp1 signaling pathways. The viral nucleocapsid protein, nonstructural protein 1 (nsp1), and nsp10 were shown to enhance CD83 promoter activity. Amino acids R43 and K44 of the N protein, as well as residues 192 to 196 (P192-5) and 214 to 216 (G214-3) of nsp10, play important roles in CD83 promoter activation. These findings provide new insights into the molecular mechanism of immune suppression by PRRSV.

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Section: Discussionmentioning

confidence: 99%

“…Sandwich ELISA. sCD83 levels were determined using a sandwich ELISA (36,39,55,68). Ninety-sixwell plates were precoated with a polyclonal rabbit antibody to the CD83 C terminus (3 g/ml; Abcam, Cambridge, United Kingdom) at 4°C overnight and then blocked with 10% nonfat dry milk in phosphatebuffered saline (PBS) prior to sample application.…”

Section: Methodsmentioning

confidence: 99%

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

Chen

Zhang

Bai

et al. 2017

J Virol

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“…Recently, the soluble CD83 (sCD83) molecule has been demonstrated to exert strong anti-inflammatory reactions and can act as an immuno-suppressive mediator to regulate the activation and maturation of dendritic cells (DCs) and monocytes 20 , 21 . Moreover, it has been reported to be a potential therapeutic agent for use in the treatment of autoimmune diseases 21 – 25 .…”

Section: Introductionmentioning

confidence: 99%

“…In turn, mCD83 is hydrolyzed by enzymes to product sCD83, which is secreted to regulate the maturation of NK cells. Elevated sCD83 binds with myeloid differentiation factor-2 (MD-2) to alter the TLR-4 signaling pathway to regulate the function of CD14+ monocytes 28 and reduces expression levels of CD1a, CD80, CD86 and MHC II to inhibit monocyte differentiation into DCs 20 . sCD83 can also induce tolerogenic DCs and reduce the expressions of CD40, CD80 and CD83 on DCs, and, in this way, alter the maturation of DCs 21 , 22 , 27 .…”

Section: Introductionmentioning

confidence: 99%

NK cells are negatively regulated by sCD83 in experimental autoimmune uveitis

Lin

Man

et al. 2017

Sci Rep

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Natural killer (NK) cells represent a subset of lymphocytes that contribute to innate immunity and have been reported to play a role in autoimmune uveitis. However, the mechanisms regulating NK cellular function in this condition remain unclear. Herein, we investigated the status of NK cells in experimental autoimmune uveitis (EAU). We found that the number of CD83+CD3−NK1.1+ cells was increased in the inflamed eyes and spleens of the EAU mouse model. At the recovery stage of EAU, serum concentrations of soluble CD83 (sCD83) were increased. sCD83 treatment relieved retinal tissue damage and decreased the number of infiltrating NK cells in inflamed eyes. Further analysis of the effects of sCD83 treatment in EAU revealed that it reduced: 1) the expressions of CD11b and CD83 in NK cells, 2) the percent of CD11bhighCD27lowCD3−NK1.1+ cells and 3) the secretion of granzyme B, perforin and IFN-γ in NK cells as demonstrated both in vivo and in vitro. When sCD83 treated-NK cells were transferred into EAU mice, retinal tissue damage was relieved. These results demonstrate sCD83 down-regulate NK cellular function and thus provide important, new information regarding the means for the beneficial effects of this agent in the treatment of autoimmune uveitis.

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“…In contrast, sCD83 functions as a suppressor of T cell activation [ 11 ]. A recent study has shown that sCD83 suppresses the differentiation of DCs from monocytes [ 12 ]. Elevated levels of plasma sCD83 have been demonstrated in patients with hematological malignancies [ 13 ].…”

Section: Introductionmentioning

confidence: 99%

Human T-cell leukemia virus type-I Tax induces the expression of CD83 on T cells

et al. 2015

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BackgroundCD83, a cell surface glycoprotein that is stably expressed on mature dendritic cells, can be transiently induced on other hematopoietic cell lineages upon cell activation. In contrast to the membrane form of CD83, soluble CD83 appears to be immunosuppressive. In an analysis of the phenotype of leukemic CD4+ T cells from patients with adult T-cell leukemia (ATL), we found that a number of primary CD4+ T cells became positive for cell surface CD83 after short-term culture, and that most of these CD83+ CD4+ T cells were positive for human T-cell leukemia virus type-I (HTLV-I) Tax (Tax1). We hypothesized that Tax1 is involved in the induction of CD83.ResultWe found that CD83 was expressed selectively on Tax1-expressing human CD4+ T cells in short-term cultured peripheral blood mononuclear cells (PBMCs) isolated from HTLV-I+ donors, including ATL patients and HTLV-I carriers. HTLV-I-infected T cell lines expressing Tax1 also expressed cell surface CD83 and released soluble CD83. CD83 can be expressed in the JPX-9 cell line by cadmium-mediated Tax1 induction and in Jurkat cells or PBMCs by Tax1 introduction via infection with a recombinant adenovirus carrying the Tax1 gene. The CD83 promoter was activated by Tax1 in an NF-κB-dependent manner. Based on a previous report showing soluble CD83-mediated prostaglandin E2 (PGE2) production from human monocytes in vitro, we tested if PGE2 affected HTLV-I propagation, and found that PGE2 strongly stimulated expression of Tax1 and viral structural molecules.ConclusionsOur results suggest that HTLV-I induces CD83 expression on T cells via Tax1 -mediated NF-κB activation, which may promote HTLV-I infection in vivo.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-015-0185-1) contains supplementary material, which is available to authorized users.

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Soluble CD83 inhibits human monocyte differentiation into dendritic cells in vitro

Cited by 19 publications

References 30 publications

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

The Nucleocapsid Protein and Nonstructural Protein 10 of Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus Enhance CD83 Production via NF-κB and Sp1 Signaling Pathways

NK cells are negatively regulated by sCD83 in experimental autoimmune uveitis

Human T-cell leukemia virus type-I Tax induces the expression of CD83 on T cells

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