Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

Ma, Xiao‐Jun; Tian, Dai-Shi; Xu, Dong; Yang, Dong; Zhu, Huifen; Liang, Zhenglun; Zhang, Zhenggang

doi:10.3748/wjg.v13.i7.1060

Cited by 29 publications

(29 citation statements)

References 25 publications

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“…However, it is controversial whether DC activated by MSU crystals always induce CTL following the process of cross-presentation. (8,(22)(23)(24) Ma et al showed that uric acid crystals promote DC to produce IL-12 and enhance the T-helper (Th)1 immune response in mice. (23) Meanwhile, Behrens et al showed that crystalline uric acid blocked tumor growth by inducing antibodies, which depended on Th2 CD4 + cells but not CD8 + lymphocytes in mice.…”

Section: Discussionmentioning

confidence: 99%

“…(8,(22)(23)(24) Ma et al showed that uric acid crystals promote DC to produce IL-12 and enhance the T-helper (Th)1 immune response in mice. (23) Meanwhile, Behrens et al showed that crystalline uric acid blocked tumor growth by inducing antibodies, which depended on Th2 CD4 + cells but not CD8 + lymphocytes in mice. (24) Because we have not investigated the detailed mechanism whereby MSU leads DC toward the crosspresentation of CTL, further study will be needed to clarify the effect of MSU crystals on T cells.…”

Section: Discussionmentioning

confidence: 99%

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Binding of monosodium urate crystals with idiotype protein efficiently promote dendritic cells to induce cytotoxic T cells

et al. 2008

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Monosodium urate (MSU) crystals have been reported to evoke specific cell immunity and to work as an adjuvant in a mouse model. The crystals also have another unique characteristic to bind with positively charged proteins, which could help to deliver some antigens into human dendritic cells (DC). We focused on the application of MSU crystals as not only an adjuvant but also as a carrier of positively charged antigenic protein to induce human cytotoxic T cells (CTL) efficiently in vitro. We selected human leukocyte antigen (HLA)-A2 expressing the multiple myeloma IM-9 cell line and its product idiotype (Id) protein as one of the best pairs of target cells and positively charged tumor-specific antigen, respectively. Following the sensitization of DC derived from HLA-A2-positive volunteers pulsed with tumor-specific monoclonal immunoglobulin G-Fab fragments (IM-9 Fab) attached to MSU crystals, the DC-stimulated CD8 + T cells killed significantly more target cells (40.1 ± 1.7%) than those stimulated by DC pulsed with MSU crystals alone (6.2 ± 8.6%, P < 0.01) or IM-9 Fab alone (4.7 ± 8.1%, P < 0.01). These cytotoxic effects of the DC-stimulated CD8 + cells were reduced when MSU crystals were precoated with fetal bovine serum. In addition, we confirmed that MSU crystals facilitated human DC to express the maturation marker, CD83 and deliver ( T umor-specific immunotherapy can open the way for an alternative approach for patients with hematological malignancies. Studies have shown that cell therapy using sensitized dendritic cells (DC) resulted in good responses in follicular lymphoma, in which tumor-producing idiotype protein (Id) was used as the specific antigen.(1,2) Multiple myeloma seems to be another promising candidate for cell immunotherapy using idiotype proteins, because the monoclonal immunoglobulin secreted into serum by myeloma cells is easily obtained for use as a tumor-specific antigen. Administration of DC pulsed with Id proteins has been clinically performed in a few studies, however, the results were disappointing because the response cases were very limited. (3)(4)(5) The reason why the ideal T-cellmediated immune responses could not be achieved is the functional deficiency of circulating DC (6,7) or lower immunogenicity of autologous Id proteins. For successful tumor-specific immunotherapy, it is necessary to develop an efficient method for DC to recognize tumor-specific Id proteins and then become mature and activated.Although monosodium urate monohydrate (MSU) is famous as the causative crystals that induce gouty arthritis, its action as a key substance in local immunoreactions has only been studied in recent years. MSU released from locally damaged cells works as an endogenous danger signal to antigen-presenting cells. (8) Depending on uric acid concentration, s.c. administered MSU crystals exhibit adjuvant activities to reduce tumor burden in vivo.(9) In addition, MSU crystals have shown another unique characteristic as they bind a lot of serum (10) or cell-surface proteins due to their negative...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Binding of monosodium urate crystals with idiotype protein efficiently promote dendritic cells to induce cytotoxic T cells

et al. 2008

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“…The same group later showed that uric acid participates in the activation of CD8 T cells to transplanted cells [36]. More recent studies have shown that uric acid can directly activate T cells [37] and enhances the T cell responses to dendritic cell-based vaccines [38]. Uric acid also potentiates B cell immune responses [39], and can activate the IL-1 receptor on monocytes via a Toll Uric acid and renal allograft dysfunction receptor pathway involving MyD88-dependent signaling [40].…”

Section: Reviewmentioning

confidence: 98%

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

Mazzali¹,

Kazamel²,

Johnson³

2010

Arab J. Nephr. Trans

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“…T-cells were cultured for 48 h at a density of 1x10 6 cells/well in 12 well-plates or 1x10 5 cells/well in 96 well-plates. Cells were cultured with or without urate at a concentration of 10 mg/dl (Sigma-Aldrich; Merck KGaA).…”

Section: Methodsmentioning

confidence: 99%

Urate crystals directly activate the T-cell receptor complex and induce T-cell proliferation

et al. 2017

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Abstract. Uric acid is a known danger associated molecular pattern molecule able to induce inflammation following internalization of its crystals by cells of the innate immune system. By activating antigen-presenting cells, urate boosts adaptive immunity as well. Furthermore, urate crystals can induce proliferation of isolated T-cells, which are unable to phagocytose crystal particles. In light of the evidence that urate crystals can also activate dendritic cells and macrophages without prior internalization but through sequestration of lipid rafts (and consequently receptors clustering in a non specific manner), the authors evaluated whether such a mechanism is involved in the direct activation of T-cells by urate crystals. In the present study, isolated human T-cells were cultured with or without urate at a concentration above its crystallization level. The expression and phosphorylation state of the T-cell receptor (TCR) complex zeta chain and the expression of the master regulator of cell proliferation c-Myc were assessed by western blotting. T-cell proliferation was measured by bromodeoxyuridine assay. Collectively, the results indicated that urate increased zeta chain phosphorylation indicating that it induces activation of TCR complex directly, since zeta chain phosphorylation takes place at the cell membrane and is a very proximal event in TCR complex-mediated signal transduction. In parallel, urate increased the expression of the transcription factor c-Myc and induced T-cell proliferation. In conclusion, urate crystals directly activate the TCR complex and induce T-cell proliferation.

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Uric acid enhances T cell immune responses to hepatitis B surface antigen-pulsed-dendritic cells in mice

Cited by 29 publications

References 25 publications

Binding of monosodium urate crystals with idiotype protein efficiently promote dendritic cells to induce cytotoxic T cells

Binding of monosodium urate crystals with idiotype protein efficiently promote dendritic cells to induce cytotoxic T cells

Could Uric acid have a Pathogenic Role in Chronic Allograft Dysfunction?

Urate crystals directly activate the T-cell receptor complex and induce T-cell proliferation

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