Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis

Morita, Yoshitaka; Yang, Jue; Gupta, Raj; Shimizu, Koïchi; Shelden, Eric A.; Endres, Judith; Mulé, James J.; McDonagh, Kevin T.; Fox, David A.

doi:10.1172/jci11490

Cited by 185 publications

(144 citation statements)

References 39 publications

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“…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: 59%

“…Several studies have shown that prophylactic treatment with tolerogenic DCs (e.g., IL-4-transduced DCs and TNF-treated DCs) is associated with a reduced type II collagen-specific IgG2a:IgG1 ratio, indicative of a switch from a Th1 cell-driven toward a Th2 cell-driven type II collagen-specific immune response (17,18). In contrast, we did not observe such a change in the type II collagen-specific antibody isotype ratio after tolerogenic DC treatment.…”

Section: Discussionmentioning

confidence: 99%

“…DCs with potent and stable tolerogenic activity can be generated in vitro by genetic or pharmacologic modification (14). For instance, DCs transduced with FasL or IL-4 have been used to prevent CIA and to inhibit arthritis symptoms in mice with established disease (15)(16)(17). Tolerogenic DCs modified by drugs (dexamethasone; Bay 11-7082) or cytokines (tumor necrosis factor [TNF]) have been used successfully to prevent the onset of CIA (18)(19)(20)(21)(22) or to suppress established arthritis in a different model, the antigeninduced arthritis model (23).…”

Section: Conclusion Treatment With Type II Collagenpulsed Tolerogenimentioning

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

123

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: Discussioncontrasting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Section: Conclusion Treatment With Type II Collagenpulsed Tolerogenimentioning

confidence: 99%

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

123

114

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“…The ability of IL-4 to inhibit proinflammatory mediator expression has led investigators to test therapeutic gene transfer to deliver IL-4 directly to joints in experimental arthritis. In these studies, either directly delivering the IL-4 gene to the joint or transducing cells to express IL-4 suppresses CIA (11,12,30,31).…”

Section: Discussionmentioning

confidence: 99%

Interleukin‐4 regulates proteoglycan‐induced arthritis by specifically suppressing the innate immune response

Cao¹,

Brombacher²,

Tunyogi-Csapó³

et al. 2007

Arthritis & Rheumatism

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Objective. Interleukin-4 (IL-4) is an antiinflammatory cytokine that inhibits the onset and severity of proteoglycan-induced arthritis (PGIA). To distinguish the role of IL-4 in the innate immune response versus the adaptive immune response, we generated mice with a specific deletion of the IL-4 receptor ␣-chain (IL-4R␣) in macrophages and neutrophils.Methods. To obtain mice in which IL-4R␣ is deleted in macrophages and neutrophils, we inter- Conclusion. These findings indicate that IL-4 functions as a major antiinflammatory cytokine in PGIA by governing the activity of macrophages/ neutrophils and less so by controlling T cell activity and autoantibody isotype expression.

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Concepts in Genetic Medicine

Dropulić¹,

Carter²

2007

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Dendritic cells genetically engineered to express IL-4 inhibit murine collagen-induced arthritis

Cited by 185 publications

References 39 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

Interleukin‐4 regulates proteoglycan‐induced arthritis by specifically suppressing the innate immune response

Concepts in Genetic Medicine

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