Modulation of established murine collagen-induced arthritis by a single inoculation of short-term lipopolysaccharide-stimulated dendritic cells

Salazar, Lorena; Aravena, Octavio; Abello, Paula; Escobar, Alejandro; Contreras-Levicoy, Juan; Rojas-Colonelli, Nicole; Catalán, Diego; Aguirre, Adam; Zúñiga, Roberto Ariel Abeldaño; Pesce, Bárbara; González, Carlos; Cepeda, Raquel; Cuchacovich, Miguel; Molina, Marı́a; Salazar‐Onfray, Flavio; Delgado, Mario; Toes, René E. M.; Aguillón, Juan Carlos

doi:10.1136/ard.2007.072199

Cited by 36 publications

(47 citation statements)

References 36 publications

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“…This is consistent with results published by Salazar et al (30) but in contrast to the results of other studies using IL-4-transduced DCs (15,16). A possible explanation for this discrepancy is THERAPEUTIC EFFECT OF TOLEROGENIC DCs IN CIA 3663 that the IL-4-transduced DCs were not matured with LPS.…”

Section: Discussionsupporting

confidence: 91%

“…Previous studies focused on the ability of tolerogenic DCs to inhibit Th1 cell responses (15,(17)(18)(19)30). In contrast, we observed an improvement in arthritis without an effect on Th1 cell responses.…”

Section: Discussioncontrasting

confidence: 57%

“…Salazar et al have reported similar results in this respect. The tolerogenic DCs used by those investigators, which were generated by short-term LPS treatment, also inhibited established arthritis without changing the IgG2a:IgG1 ratio; however, their tolerogenic DC treatment did inhibit IFN␥ production (30). Earlier studies of anti-TNF treatment of established arthritis also did not show a change in the IgG2a:IgG1 ratio (41,42).…”

Section: Discussionmentioning

confidence: 96%

“…The data shown in Table 1 demonstrate that, based on the various doses, routes, and number of injections tested, 3 intravenous injections with 1 ϫ 10 6 tolerogenic DCs was the optimal tolerogenic DC treatment regimen. However, data from other studies indicate that optimal treatment regimens are different for other types of tolerogenic DCs (15,16,23,30).…”

Section: Discussionmentioning

confidence: 99%

“…Type II collagen-specific antibodies in the sera of mice with CIA are often used to examine the class of the type II collagen-specific immune response (17)(18)(19)30). Type II collagen-specific IgG2a antibodies are associated with a Th1 cell-driven immune response, whereas type II collagen-specific IgG1 antibodies are associated with a Th2 cell-driven response (18).…”

Section: Enhancement Of Il-10-positive Cd4؉ T Cells and Inhibition Ofmentioning

confidence: 99%

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Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Stoop¹,

Harry²,

Delwig³

et al. 2010

Arthritis & Rheumatism

124

114

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Results. Tolerogenic DCs displayed a semimature phenotype, produced low levels of inflammatory cytokines, and exhibited low T cell stimulatory capacity. Upon intravenous injection into arthritic mice, tolerogenic DCs migrated to the spleen, liver, lung, feet, and draining lymph nodes. Treatment of arthritic mice with type II collagen-pulsed tolerogenic DCs, but not unpulsed tolerogenic DCs or mature DCs, significantly inhibited disease severity and progression. This improvement coincided with a significant decrease in the number of Th17 cells and an increase in the number of interleukin-10-producing CD4؉ T cells, whereas tolerogenic DC treatment had no detectable effect on Th1 cells or interleukin-17-producing ␥/␦ T cells.Conclusion. Treatment with type II collagenpulsed tolerogenic DCs decreases the proportion of Th17 cells in arthritic mice and simultaneously reduces the severity and progression of arthritis.

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 57%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Enhancement Of Il-10-positive Cd4؉ T Cells and Inhibition Ofmentioning

confidence: 99%

See 3 more Smart Citations

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Stoop¹,

Harry²,

Delwig³

et al. 2010

Arthritis & Rheumatism

124

114

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Blocking of p38 and transforming growth factor β receptor pathways impairs the ability of tolerogenic dendritic cells to suppress murine arthritis

Gárate¹,

Rojas-Colonelli²,

Peña³

et al. 2012

Arthritis & Rheumatism

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Objective. Dendritic cells (DCs) modulated with lipopolysaccharide (LPS) are able to reduce inflammation when therapeutically administered into mice with collagen-induced arthritis (CIA). The aim of this study was to uncover the mechanisms that define the tolerogenic effect of short-term LPS-modulated DCs on CIA.Methods. Bone marrow-derived DCs were stimulated for 4 hours with LPS and characterized for their expression of maturation markers and their cytokine secretion profiles. Stimulated cells were treated with SB203580 or SB431542 to inhibit the p38 or transforming growth factor ␤ (TGF␤) receptor pathway, respectively, or were left unmodified and, on day 35 after CIA induction, were used to inoculate mice. Disease severity was evaluated clinically. CD4؉ T cell populations were counted in the spleen and lymph nodes from inoculated or untreated mice with CIA. CD4؉ splenic T cells were transferred from mice with CIA treated with LPSstimulated DCs or from untreated mice with CIA into other mice with CIA on day 35 of arthritis. Conclusion. DCs modulated short-term (4 hours) with LPS are able to confer a sustained cure in mice with established arthritis by re-educating the CD4؉ T cell populations. This effect is dependent on the p38 and the TGF␤ receptor signaling pathways, which suggests the participation of IL-10 and TGF␤ in the recovery of tolerance. Results. Treatment with LPS-stimulated DCs in-

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Effects of simvastatin on the function of dendritic cells in patients with rheumatic arthritis

Liu

Wang

Shen

et al. 2010

J. Huazhong Univ. Sci. Technol. [Med. Sci.]

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The present study examined the functional profile of dendritic cells (DCs) in patients with rheumatoid arthritis (RA) and the effects of simvastatin on the function of DCs. A total of 40 patients who was recently diagnosed as having RA were equally assigned to two groups: the routine treatment group (group R) and the routine treatment plus simvastatin group (group R+S). Twenty healthy individuals served as control. The peripheral blood mononuclear cells (PBMCs) were isolated before and 4 weeks after the treatment and then cultured with interleukin-4 (IL-4) and granulocyte-macrophage colony stimulatory factor (GM-CSF) to prepare mature DCs. The expression of co-stimulating factor CD86 on the surface of DCs was assessed by flow cytometry. And the stimulating capacity of DCs was measured by mixed lymphocyte reaction (MLR). The contents of cytokines in culture supernatants of DCs in MLR were detected by ELISA. Blood lipids and high-sensitivity C-reactive protein (hs-CRP) were detected. The relationship between the expression of CD86 and the blood CRP level was also investigated. The results showed that, as compared with the control group, the CD86 expression and the level of cytokines secreted by DCs were significantly increased in RA patients and greater stimulating capacity of DCs in MLR was demonstrated in RA patients. T lymphocytes in MLR secreted higher levels of proinflammatory cytokines (IL-2, IL-17, TNF-α and INF-γ) and lower level of anti-inflammation cytokine (IL-10). The function of DCs was markedly weakened and the level of hs-CRP and low-density lipoprotein was substantially lowered in group R+S in comparison to group R. The CD86 expression was positively correlated with hs-CRP. It was concluded that DCs in RA are highly activated and DC-initiated immune reaction may play an important role in the pathogenesis of RA. Simvastatin administration can significantly inhibit the DCs function and reduce the level of hs-CRP, indicating the suppression on inflammatory reaction may be one of the mechanisms by which simvastatin exerts its effect in treating RA.

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Modulation of established murine collagen-induced arthritis by a single inoculation of short-term lipopolysaccharide-stimulated dendritic cells

Abstract: Short-term LPS-modulated DCs inoculation interferes with CIA progression when loaded with CII.

Cited by 36 publications

References 36 publications

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Therapeutic effect of tolerogenic dendritic cells in established collagen‐induced arthritis is associated with a reduction in Th17 responses

Blocking of p38 and transforming growth factor β receptor pathways impairs the ability of tolerogenic dendritic cells to suppress murine arthritis

Effects of simvastatin on the function of dendritic cells in patients with rheumatic arthritis

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