Low Reactivity of Peripheral Blood Dendritic Cells Respond to IL-1 and GM-CSF in SLE Patients

Akiyama, Yuji; Suzuki, Tomohiko; Imai, F; Ishibashi, Toshiko; Fujimaki, Toshiaki

doi:10.1007/978-1-4615-1971-3_86

Cited by 4 publications

(3 citation statements)

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“…As stated above, this cell type could be employed for therapeutic purposes in SLE and other autoimmune diseases [3]. On the other hand, our data as well as the studies of Steinbach et al [24], and Akiyama et al [32], show that the in vitro generation of conventional DC from monocytes in SLE patients is defective. It seems evident that this phenomenon could be because of an enhanced rate of cell death or to a defective differentiation of monocytes from SLE patients.…”

Section: Discussionsupporting

confidence: 66%

Phenotypic Analysis of IL‐10‐treated, Monocyte‐derived Dendritic Cells in Patients with Systemic Lupus Erythematosus

et al. 2006

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Dendritic cells (DC) play a dual role in the immune response, participating in its induction, and the maintenance of immune tolerance. The aim of this work was to perform a quantitative and phenotypic analysis of DC generated in vitro in the presence of IL‐10 in patients with systemic lupus erythematosus (SLE). Blood samples were obtained from 10 active and untreated patients with SLE and six controls. Monocyte‐derived DC were generated in vitro in the presence or absence of IL‐10, and a quantitative and phenotypic analysis was performed. We found that freshly isolated monocytes from SLE patients had an increased expression of CD11b. On the other hand, the efficiency of in vitro DC generation was diminished in blood samples from SLE patients for conventional DC, but not for IL‐10‐treated DC. A diminished expression of HLA‐DR, CD9 and CD86 was observed in conventional DC from SLE patients compared with controls. In contrast, enhanced levels of HLA‐DR, CD80, CD9 and CD151 tetraspanins, FN1 (a class II MHC‐tetraspanin epitope), CD85j/ILT2 and CD69 were detected in IL‐10‐treated DC from SLE patients. Accordingly, the phenotypic profile of IL‐10‐treated DC was very different in SLE and controls. However, the synthesis of IL‐10 and IL‐12 was similar in IL‐10‐treated and conventional cells in both SLE patients and controls. Our findings on the aberrant phenotype of IL‐10‐treated DC in SLE and their normal efficiency of in vitro generation may be important for the design of future therapies of this condition based on the administration of DC to induce immune tolerance.

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Section: Discussionsupporting

confidence: 66%

Phenotypic Analysis of IL‐10‐treated, Monocyte‐derived Dendritic Cells in Patients with Systemic Lupus Erythematosus

et al. 2006

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“…Recently, responses of the peripheral blood dendritic cells to IL-1 or GM-CSF have been shown to be reduced in SLE, although its mechanism has not been clear. 10 In the normal controls, expression of the CD80 increased during the culture with FCS-supplemented medium, and increased further by IFN-g or GM-CSF but not by IL-4. Also in the SLE patients, it increased during the culture with medium alone and further increased by IFN-g while less than that in the normal controls.…”

Section: Discussionmentioning

confidence: 91%

Dysregulation of the granulocyte-macrophage colony stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus

Funauchi

Yoo²,

Nozaki³

et al. 2002

Lupus

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CD80 and CD86, expressed on the antigen-presenting cells (APCs) provide costimulatory signals for T lymphocytes. Recently, defective expression of CD80 has been reported in systemic lupus erythematosus (SLE) although its mechanism is unclear. Here, expression of the B7 antigens induced by interferon-gamma, interleukin-4 or granulocyte-macrophage stimulating-factor (GM-CSF) along the differentiation process of APCs was investigated. In contrast to CD86, expression of CD80 on the CD14+ cells induced by GM-CSF was reduced in SLE. GM-CSF receptor (GM-CSFR) was down-regulated by GM-CSF or phorbol 12-myristate 13-acetate in both of the normal controls and SLE patients, while this change was more remarkable in the latter. In the presence of 1-(5-isoquinolinsulfonyl)-2-methylpiperazine, an inhibitor of protein kinase C, the PMA-induced down-regulation of GM-CSFR was reversed in the normal controls but not in SLE. These data suggest that dysregulation of the GM-CSFR might be associated with the defective expression of CD80, leading to dysfunction of the APCs in SLE.

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“…GM-CSF can also be produced locally by glomerular mesangial cells and levels correlate with lupus nephritis ( 131 ). Interestingly, some studies suggest that neutrophils and dendritic cells may demonstrate resistance to GM-CSF responses in SLE ( 143 , 144 ). Colony formation by splenic progenitor cells induced by GM-CSF is increased in Lyn −/− mice ( 15 ).…”

Section: Targeting Inflammation In Lupusmentioning

confidence: 99%

Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

2015

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Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known outcomes or the potential for targeting these factors in SLE.

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Low Reactivity of Peripheral Blood Dendritic Cells Respond to IL-1 and GM-CSF in SLE Patients

Cited by 4 publications

References 0 publications

Phenotypic Analysis of IL‐10‐treated, Monocyte‐derived Dendritic Cells in Patients with Systemic Lupus Erythematosus

Phenotypic Analysis of IL‐10‐treated, Monocyte‐derived Dendritic Cells in Patients with Systemic Lupus Erythematosus

Dysregulation of the granulocyte-macrophage colony stimulating factor receptor is one of the causes of defective expression of CD80 antigen in systemic lupus erythematosus

Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

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