Impaired IFN-α secretion by plasmacytoid dendritic cells induced by TLR9 activation in chronic idiopathic urticaria

Futata, E.; Azor, Mayce Helena; Santos, Julia dos; Maruta, Celina Wakisaka; Sotto, Mírian Nacagami; Guedes, Fernanda; Rivitti, Evandro A.; Duarte, Adriana Pereira; Sato, Maria Notomi

doi:10.1111/j.1365-2133.2010.10198.x

Cited by 30 publications

(18 citation statements)

References 44 publications

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“…The investigation of early events of innate immunity through the study of dendritic cells that link innate and adaptive immune system has provided insights into the dysregulated immune response in chronic urticaria [44]. Plasmacytoid dendritic cells (pDC) express toll-like receptors (TLR) that are activated by natural and synthetic ligands triggering proinflammatory responses that play a key role in the pathogenesis of several inflammatory disorders including urticaria [45].…”

Section: Chronic Urticaria: Immune Mediated Inflammatory Disordermentioning

confidence: 99%

“…Accordingly, a study of early events of the immune response, through the activation of pDC by TLR sensing, was undertaken to evaluate immune dysregulation in chronic urticaria [44]. …”

Section: Chronic Urticaria: Immune Mediated Inflammatory Disordermentioning

confidence: 99%

“…A normal degree of activation of pDC by the expression of costimulatory molecules and an increased constitutive STAT 1 phosphorylation on nonstimulated lymphocytes was observed. However, IFN-alpha secretion by pDC upon stimulation by CpGA was impaired and it was associated with altered IRF-7 and downregulation of TLR 9 expression, indicating a functional impairment of pDC, and was supportive of immune dysregulation in CU [44]. …”

Section: Chronic Urticaria: Immune Mediated Inflammatory Disordermentioning

confidence: 99%

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Pathogenesis of Chronic Urticaria: An Overview

Jain

2014

Dermatology Research and Practice

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The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria.

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Section: Chronic Urticaria: Immune Mediated Inflammatory Disordermentioning

confidence: 99%

“…Accordingly, a study of early events of the immune response, through the activation of pDC by TLR sensing, was undertaken to evaluate immune dysregulation in chronic urticaria [44]. …”

Section: Chronic Urticaria: Immune Mediated Inflammatory Disordermentioning

confidence: 99%

Section: Chronic Urticaria: Immune Mediated Inflammatory Disordermentioning

confidence: 99%

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Pathogenesis of Chronic Urticaria: An Overview

Jain

2014

Dermatology Research and Practice

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“…This possibility is consistent with a recent study showing that stimulation of TLR9 on DCs reduces IFN-α secretion. 39 Several lines of evidence suggest that the elevation in IFN-α that we observed in atherosclerotic lesions of the TLR9-deficient mice (an increase in the plasma level was not seen, data not shown) can contribute to the augmentation in lesion growth. Low-dose IFN-α treatment accelerated atherosclerosis in LDL receptor-deficient mice.…”

Section: Vldl/ldl: Hdl (Ratio)mentioning

confidence: 99%

Protective Role for Toll-Like Receptor-9 in the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice

Koulis

Chen

Hausding

et al. 2014

ATVB

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Objective— Atherosclerosis is driven by inflammatory reactions that are shared with the innate immune system. Toll-like receptor-9 (TLR9) is an intracellular pattern recognition receptor of the innate immune system that is currently under clinical investigation as a therapeutic target in inflammatory diseases. Here, we investigated whether TLR9 has a role in the development of atherosclerosis in apolipoprotein E–deficient (ApoE −/− ) mice. Approach and Results— Newly generated double-knockout ApoE −/− :TLR9 −/− mice and control ApoE −/− mice were fed a high-fat diet from 8 weeks and effects on lesion size, cellular composition, inflammatory status, and plasma lipids were assessed after 8, 12, 15, and 20 weeks. All 4 time points demonstrated exacerbated atherosclerotic lesion severity in ApoE −/− :TLR9 −/− mice, with a corresponding increase in lipid deposition and accumulation of macrophages, dendritic cells, and CD4 + T cells. Although ApoE −/− :TLR9 −/− mice exhibited an increase in plasma very low-density lipoprotein/low-density-lipoprotein cholesterol, the very low-density lipoprotein/low-density lipoprotein:high-density lipoprotein ratio was unaltered because of a parallel increase in plasma high-density lipoprotein cholesterol. As a potential mechanism accounting for plaque progression in ApoE −/− :TLR9 −/− mice, CD4 + T-cell accumulation was further investigated and depletion of these cells in ApoE −/− :TLR9 −/− mice significantly reduced lesion severity. As a final translational approach, administration of a TLR9 agonist (type B CpG oligodeoxynucleotide 1668) to ApoE −/− mice resulted in a reduction of lesion severity. Conclusions— Genetic deletion of the innate immune receptor TLR9 exacerbated atherosclerosis in ApoE −/− mice fed a high-fat diet. CD4 + T cells were identified as potential mediators of this effect. A type B CpG oligodeoxynucleotide TLR9 agonist reduced lesion severity, thus identifying a novel therapeutic approach in atherosclerosis.

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“…При стимуляции TLR9 лигандом CpG тип А не происходил адекватный синтез интерферона альфа дендритными клетка-ми у пациентов с хронической крапивницей [39].…”

Section: ) иммунная активация тучных клеток при хро-нической крапивницеunclassified

Chronic Urticarial in Childhood. Immune Pathology of Chronic Urticarial in Children (Part I)

2014

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Резюме. В данной части обзора рассмотрены распространенность, генетические факторы пред-расположенности и некоторые иммунологические механизмы хронической крапивницы у детей. Показано, что тучным клеткам и базофилам принадлежит центральная роль в патогенезе всех форм. В ходе воспалительных реакций при хроническом течении крапивницы происходит стимуляция про-дукции таких цитокинов, как CCL2, CХCL8, IL-1, IL-4, IL-6, IL-10, IL-13, IL-17. Активация туч-ных клеток и базофилов реализуется через специфические рецепторы на мембране клеток. Особое место занимает аутоиммунная крапивница, в патогенезе которой участвуют анти-FCεRIα антитела или аутоантитела к IgE, оказывающие гистамино-высвобождающее действие за счет перекрестного связывания α-цепей высокоаффинного IgE рецептора или перекрестного связывания фиксирован-ных на тучных клетках IgE. Дегрануляция базофилов сопровождается появлением активационных молекул -СD203с, CD63. Экспрессию СD203с ряд авторов считает косвенным признаком аутоим-мунного процесса, при наличии положительного теста с аутосывороткой. Повышение экспрессии лиганда CD40L на поверхности активированных Т-лимфоцитов свидетельствует об усилении сигна-лов для активации В-лимфоцитов и синтеза аутоантител.Ключевые слова: хроническая крапивница, цитокины, базофилы, CD203c

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Impaired IFN-α secretion by plasmacytoid dendritic cells induced by TLR9 activation in chronic idiopathic urticaria

Abstract: The findings showed an innate immune response in CIU disturbed by impairment of the pDC response to TLR9 activation.

Cited by 30 publications

References 44 publications

Pathogenesis of Chronic Urticaria: An Overview

Pathogenesis of Chronic Urticaria: An Overview

Protective Role for Toll-Like Receptor-9 in the Development of Atherosclerosis in Apolipoprotein E–Deficient Mice

Chronic Urticarial in Childhood. Immune Pathology of Chronic Urticarial in Children (Part I)

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