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

Li, Jianguo; Du, Yumo; Yan, Zhidong; Jia, Yan; Zhuansun, Yongxun; Chen, Rui; Zhang, Wei; Feng, Suling; Ran, Pixin

doi:10.3892/etm.2016.2989

Cited by 56 publications

(49 citation statements)

References 38 publications

(41 reference statements)

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“…A deeper characterization of lung immune cells revealed that cDCs, moDCs and T cells were recruited in lower numbers to the lungs of allergic HFD‐fed mice as compared to CD mice. Interestingly, pulmonary DCs from CD or HFD‐fed mice were equally potent to expand T cells with Th2 polarization profile, which depends on CD86/CD80 costimulation, suggesting the CD86/CD80 axis not to be affected in our model. In contrast, CD11b + cDCs express lower numbers of MHC‐II and the costimulatory molecule CD40 upon HFD feeding compared to CD.…”

Section: Discussionmentioning

confidence: 76%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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Background A close association between obesity and asthma has been described. The nature of this association remains elusive, especially with respect to allergic asthma. Controversial findings exist regarding the impact of short‐term high‐fat diet (HFD) feeding on the development of allergic asthma. Objective To delineate the impact of short‐term HFD feeding on the development of experimental allergic asthma. Methods Female C57BL/6JRJ mice were fed with a short‐term HFD or chow diet (CD) for 12 weeks. Allergic asthma was induced by intraperitoneal OVA/alum sensitization followed by repeated OVA airway challenges. We determined airway hyperresponsiveness (AHR) and pulmonary inflammation by histologic and flow cytometric analysis of immune cells. Furthermore, we assessed the impact of HFD on dendritic cell (DC)‐mediated activation of T cells. Results Female mice showed a mild increase in body weight accompanied by mild metabolic alterations. Upon OVA challenge, CD‐fed mice developed strong AHR and airway inflammation, which were markedly reduced in HFD‐fed mice. Mucus production was similar in both treatment groups. OVA‐induced increases in DC and CD4+ T‐cell recruitment to the lungs were significantly attenuated in HFD‐fed mice. MHC‐II expression and CD40 expression in pulmonary CD11b+ DCs were markedly lower in HFD‐fed compared to CD‐fed mice, which was associated in vivo with a decreased T helper (Th) 1/17 differentiation and Treg formation without impacting Th2 differentiation. Conclusions/clinical relevance These findings suggest that short‐term HFD feeding attenuates the development of AHR, airway inflammation, pulmonary DC recruitment and MHC‐II/CD40 expression leading to diminished Th1/17 but unchanged Th2 differentiation. Thus, short‐term HFD feeding and associated metabolic alterations may have protective effects in allergic asthma development.

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Section: Discussionmentioning

confidence: 76%

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Schröder

Wiese

Ender

et al. 2019

Clin Experimental Allergy

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“…It is widely accepted that the cytokines secreted by the T cells shape the outcome of the immune response [11]. We detected cytokines in the supernatant of the cocultured T cells of different types of imDCs.…”

Section: Ccr7 Overexpression and Relb Kd In Imdcs Induced A Shift Fromentioning

confidence: 85%

Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model

Dong

Chen

Yuan³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Skin transplantation aims to cover skin defects but often fails due to immune rejection of the transplantated tissue. Immature dendritic cells (imDCs) induce immune tolerance but have a low migration rate. After stimulation, imDCs transform into mature DCs, which activate immune rejection. Thus, inducing imDC to obtain a high migration counteracts development of immune tolerance. Methods & Results: We transfected imDCs with a recombinant adenovirus carrying the CCR7 gene (Ad-CCR7) and a small interfering RNA targeting RelB (RelB-siRNA) to concurrently overexpress CCR7 and downregulate RelB expression. Functionally, such cells showed a significantly enhanced migration rate in the chemotactic assay and decreased T-cell proliferation after lipopolysaccharide stimulation in mixed lymphocyte reactions. Cotransfected cells showed an increased ability to induce immune tolerance by upregulating T regulatory (Treg) cells and shifting the Th1/Th2 ratio. Cotransfection of Ad-CCR7 and RelB-siRNA endowed imDCs with resistance to apoptosis and cell death. CCR7 overexpression and RelB knockdown (KD) in imDCs improve skin-graft survival in a murine skin-transplantation model. Conclusion: Transfection with Ad-CCR7 and RelB KD in imDCs may be an effective approach inducing immune tolerance, thus being potentially valuable for inhibiting allograft rejection.

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“…Li et al [8] reported that IFN-γ production by mouse T cells cocultured with DCs transfected with CD80 and DC86 siRNAs increased significantly, and that IL-4 production decreased significantly. CD86 was also required for the development of IL-4-producing T cells in a murine model [9].…”

mentioning

confidence: 99%

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

Suzuki

Yokota

Matsumoto

et al. 2018

Int Arch Allergy Immunol

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Background: We previously reported that siRNA-induced CD40-silenced dendritic cells (DCs) inhibit allergic responses and symptoms. However, more potent therapies are needed. To our knowledge, synergic effects of gene silencing in DCs by ≥2 siRNAs have not been reported to control allergic diseases. Therefore, we investigated the synergistic effects of the silencing of CD40 and CD86 in DCs on allergic responses. Methods: Mice were treated with CD40/CD86-silenced DCs, which were transfected with CD40/CD86 siRNAs and pulsed with ovalbumin (OVA) antigen. The effects of these DCs on allergic symptoms and allergic responses were estimated. Results: The administration of CD40/CD86-silenced OVA-pulsed DCs significantly inhibited the number of sneezes and nasal rubbing movements, the number of eosinophils in the nasal mucosa, and the level of OVA-specific IgE when compared with those for CD40- or CD86-silenced OVA-pulsed DCs alone (p < 0.01). These inhibitory effects were detected before sensitization as well as after the establishment of allergic rhinitis. CD40/CD86-silenced OVA-pulsed DCs did not inhibit KLH-induced allergies. Foxp3 gene expression was significantly upregulated in CD40-silenced DCs compared to in CD86-silenced DCs (p < 0.01). IL-4 production by T cells was suppressed more substantially when using CD86-silenced DCs than with CD40-silenced DCs (p < 0.01). Conclusions: These results indicate, for the first time, that siRNA-induced CD40/CD86-silenced antigen-specific DCs have greater inhibitory effects against allergic responses than those of CD40- or CD86-silenced antigen-specific DCs alone. This study also suggests that the synergic effects of gene silencing in DCs by ≥2 siRNAs are useful for the control of allergic diseases. Thus, owing to the synergistic effects, CD40 and CD86 silencing has the potential to substantially improve the treatment of allergic diseases.

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

Cited by 56 publications

References 38 publications

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Short‐term high‐fat diet feeding protects from the development of experimental allergic asthma in mice

Concurrent CCR7 Overexpression and RelB Knockdown in Immature Dendritic Cells Induces Immune Tolerance and Improves Skin-Graft Survival in a Murine Model

Synergic Effects of CD40 and CD86 Silencing in Dendritic Cells on the Control of Allergic Diseases

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