Role of Dendritic Cells in Atopic Dermatitis: An Update

Bieber, Thomas; Novak, Natalija; Herrmann, Nadine; Koch, Susanne

doi:10.1007/s12016-010-8224-0

Cited by 24 publications

(25 citation statements)

References 34 publications

(39 reference statements)

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“…IFN, interferon; IL, interleukin; mDC, mature dendritic cell; siRNA, small interfering RNACD, cluster of differentiation. the promotion of Th2-cell activation (26)(27)(28). The first signal is the formation of antigen-MHC complexes on the mDC surface that bind specifically with the T-cell receptor-CD3 receptor complex on T-cell surfaces, and the second signal is co-stimulatory molecule expression and functional activation on the mDC surfaces that specifically bind to receptors on naïve T cells; the two signals form a co-stimulatory pathway (29).…”

Section: Discussionmentioning

confidence: 99%

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Yan

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Dendritic cells (DCs) are associated with the activation and differentiation of T helper (Th) cells. Cluster of differentiation (CD)80 and CD86, the co-stimulatory molecules highly expressed in DCs, have are prominent in promoting the differentiation of Th cells toward Th2 cells. However, little is known about the effect of CD80 and CD86 knockdown on Th1/Th2 cytokine production in mature DCs (mDCs). The aim of the present study was to investigate whether small-interfering RNA (siRNA) could suppress the surface expression of CD80 and CD86 in mDCs. The effects of CD80 and CD86 knockdown in mDCs on Th1/Th2 cytokine expression were examined using an asthmatic murine model. DCs were isolated, separated and cultured in vitro. Flow cytometry was used to examine the expression of CD11c, CD80 and CD86 on the DCs. The DCs were transfected with CD80-and CD86-specific siRNA, while non-siRNA and negative siRNA controls were also designed. Then, the mRNA and protein expression levels of CD80 and CD86 were determined by reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. The levels of interferon (IFN)-γ and interleukin (IL)-4 produced by T cells co-cultured with mDCs were measured by enzyme-linked immunosorbent assay. Substantial downregulation of CD80 and CD86 mRNA and protein levels were observed in the mDCs following transfection with siRNA. The level of IFN-γ produced by T cells co-cultured with mDCs was significantly increased in the siRNA group, while IL-4 production was significantly decreased. These results show that specific targeting of CD80 and CD86 with siRNA is able to suppress CD80/CD86 expression and consequently regulate Th1/Th2 cytokine levels by increasing IFN-γ production and decreasing IL-4 levels in an asthmatic murine model.

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Section: Discussionmentioning

confidence: 99%

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Yan

et al. 2016

Experimental and Therapeutic Medicine

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“…Depending on how this TBI-induced cytokine microenvironment is skewed, it could greatly impact the conditioning of cDC within the skin and dictate how these cells interact with T cells in draining lymph nodes (10). Recently, it has been suggested that atopic dermatitis (AD), a chronic inflammatory skin disease, is, in part, initiated and driven by cDC (41) and patients who suffer from AD often exhibit a type 2 cytokine profile within the skin. However, despite an increased understanding in the immunopathology, AD still remains an idiopathic disease that manifests in individuals with a predetermined genetic background or in those exposed to a variety of environmental stimuli (42).…”

Section: Discussionmentioning

confidence: 99%

Exposure to Ionizing Radiation Induces the Migration of Cutaneous Dendritic Cells by a CCR7-Dependent Mechanism

Cummings

Gerber

Judge

et al. 2012

The Journal of Immunology

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In the event of a deliberate or accidental radiological emergency, the skin would likely receive substantial ionizing radiation (IR) poisoning which could negatively impact cellular proliferation, communication, and immune-regulation within the cutaneous microenvironment. Indeed, as we have previously shown, local IR exposure to the murine ear causes a reduction of two types of cutaneous dendritic cells (cDC), including interstitial DC (iDC) of the dermis and Langerhans cells (LC) of the epidermis, in a dose and time dependent manner. These APCs are critical regulators of skin homeostasis, immuno-surveillance, and the induction of T and B cell-mediated immunity as previously demonstrated using conditional cDC knockout mice. To mimic a radiological emergency, we developed a murine model of sub-lethal total body irradiation (TBI). Our data would suggest that TBI results in the reduction of cDC from the murine ear that was not due to a systemic response to IR as a loss was not observed in shielded ears. We further determined that this reduction was due, in part, to the up-regulation of the chemoattractant CCL21 on lymphatic vessels as well as CCR7 expressed on cDC. Migration as a potential mechanism was confirmed using CCR7−/− mice where cDC were not depleted following TBI. Finally, we demonstrated that the loss of cDC following TBI results in an impaired contact hypersensitivity (CHS) response to hapten by using a modified CHS protocol. Taken together, these data suggest that IR exposure may result in diminished immuno-surveillance in the skin, which could render the host more susceptible to pathogens.

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“…A possible mechanism by which genetic polymorphisms of the TLR2 gene causes impact on the binding of TLR2 ligands, such as S. aureus ‐derived proteins, herpes simplex virus, β ‐defensins, and others, leading to an altered function of mDCs in AD remains unclear . Polymorphisms of TLR9 on pDCs expressing the high‐affinity receptor for IgE (Fc ε RI) in AD individuals and the possible cross‐talk between TLR2 and Fc ε RI expressed on mDCs in AD patients may provide interesting insights regarding the role of infections in the regulation of IgE synthesis .…”

Section: Introductionmentioning

confidence: 99%

Evidence of regulatory myeloid dendritic cells and circulating inflammatory epidermal dendritic cells‐like modulated by Toll‐like receptors 2 and 7/8 in adults with atopic dermatitis

et al. 2017

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In AD individuals, classic mDC showed an immunomodulatory profile, favoring tolerance in a combined action with IDEC-like, and inducing Th1 polarization. Our findings indicate a potential role of IDEC-like in the maintenance of inflammation in atopic dermatitis patients; moreover, IDEC-like may exert a regulatory impact on T cells of AD individuals through IL-10, often induced by agonist mimicking single stranded RNA virus.

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Role of Dendritic Cells in Atopic Dermatitis: An Update

Cited by 24 publications

References 34 publications

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Exposure to Ionizing Radiation Induces the Migration of Cutaneous Dendritic Cells by a CCR7-Dependent Mechanism

Evidence of regulatory myeloid dendritic cells and circulating inflammatory epidermal dendritic cells‐like modulated by Toll‐like receptors 2 and 7/8 in adults with atopic dermatitis

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