Epigenetic Control of <i>Ccr7</i> Expression in Distinct Lineages of Lung Dendritic Cells

Moran, Timothy P.; Nakano, Hideki; Kondilis-Mangum, Hrisavgi D.; Wade, Paul A.; Cook, Donald N.

doi:10.4049/jimmunol.1401104

Cited by 26 publications

(23 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It was recently reported that histone 3 lysine 27 trimethylation (H3K27me3) modulates CCR7 expression in DCs 36 . To investigate if miR-155 regulates CCR7 expression in DCs by affecting H3K27me3, a chromatin immunoprecipitation (ChIP) assay was performed.…”

Section: Resultsmentioning

confidence: 99%

microRNA-155 deficiency impairs dendritic cell function in breast cancer

Wang

Iwanowycz

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

In antitumor immunity, dendritic cells (DCs) capture, process, and present tumor antigens to T cells, initiating a tumoricidal response. However, DCs are often dysfunctional due to their exposure to the tumor microenvironment (TME), leading to tumor escape from immune surveillance. Here, a vital role of microRNA-155 (miR-155) in regulating the function of DCs in breast cancer is reported. Host miR-155 deficiency enhanced breast cancer growth in mice, accompanied by reduced DCs in the tumors and draining lymph nodes. miR-155 deficiency in DCs impaired their maturation, migration ability, cytokine production, and the ability to activate T cells. We demonstrate that miR-155 regulates DC migration through epigenetic modulation of CCR7 expression. Moreover, IL-6 and IL-10, two cytokines abundant in the TME, are found to impair DC maturation by suppressing miR-155 expression. Furthermore, animal studies show that a lack of miR-155 diminishes the effectiveness of DC-based immunotherapy for breast cancer. In conclusion, these findings suggest that miR-155 is a master regulator of DC function in breast cancer, including maturation, cytokine secretion, migration toward lymph nodes, and activation of T-cells. These results suggest that boosting the expression of a single microRNA, miR-155, may significantly improve the efficacy of DC-based immunotherapies for breast cancer.

show abstract

Section: Resultsmentioning

confidence: 99%

microRNA-155 deficiency impairs dendritic cell function in breast cancer

Wang

Iwanowycz

et al. 2016

OncoImmunology

View full text Add to dashboard Cite

show abstract

“…Our in‐vitro experiments were performed with isolated lamina propria DC as well as with GM‐CSF matured BMDC. It is important to realize that expression of CCR7 on BMDC is lower in GM‐CSF‐derived cultures compared to FLT3L‐matured BMDC . This might imply that the differences observed could be even more pronounced when using alternative methods of cell preparation.…”

Section: Discussionmentioning

confidence: 99%

Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells

et al. 2018

View full text Add to dashboard Cite

Under homeostatic conditions, dendritic cells (DCs) continuously patrol the intestinal lamina propria. Upon antigen encounter, DCs initiate C‐C motif chemokine receptor 7 (CCR7) expression and migrate into lymph nodes to direct T cell activation and differentiation. The mechanistic underpinnings of DC migration from the tissues to lymph nodes have been largely elucidated, contributing greatly to our understanding of DC functionality and intestinal immunity. In contrast, the molecular mechanisms allowing DCs to efficiently migrate through the complex extracellular matrix of the intestinal lamina propria prior to antigen encounter are still incompletely understood. Here we show that small intestinal murine CD11b+CD103+ DCs express Placenta‐expressed transcript 1 (Plet1), a glycophoshatidylinositol (GPI)‐anchored surface protein involved in migration of keratinocytes during wound healing. In the absence of Plet1, CD11b+CD103+ DCs display aberrant migratory behavior, and accumulate in the small intestine, independent of CCR7 responsiveness. RNA‐sequencing indicated involvement of Plet1 in extracellular matrix‐interactiveness, and subsequent in‐vitro migration assays revealed that Plet1 augments the ability of DCs to migrate through extracellular matrix containing environments. In conclusion, our findings reveal that expression of Plet1 facilitates homeostatic interstitial migration of small intestinal DCs.

show abstract

“…Murine lung and LN cells were isolated and analysed by flow cytometry as previously described . Briefly, harvested lungs and mLNs were manually cut with scissors and digested with Liberase TM (100 μg/mL; Roche Diagnostics), collagenase XI (250 μg/mL), hyaluronidase 1a (1 mg/mL), and DNase I (200 μg/mL; Sigma, St. Louis, MO) for 1 hour (lungs) or 30 minutes (mLNs) at 37°C.…”

Section: Methodsmentioning

confidence: 99%

“…All antibodies were purchased from BioLegend or BD Biosciences. In some experiments, peanut uptake by lung cDCs was evaluated following instillation of peanut labelled with Alexa Fluor 647 (Invitrogen) as described previously …”

Section: Methodsmentioning

confidence: 99%

“…Murine lung and LN cells were isolated and analysed by flow cytometry as previously described. 51,52 Briefly, harvested lungs and mLNs were manually cut with scissors and digested with Liberase TM (100 μg/mL; Roche Diagnostics), collagenase XI (250 μg/mL), Flow cytometry data were acquired with a four-laser LSRII (BD Biosciences) and analysed using FlowJo (Ashland, OR) software.…”

Section: Flow Cytometric Analysis Of Lung and Ln Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Indoor dust acts as an adjuvant to promote sensitization to peanut through the airway

Smeekens

Immormino

Balogh

et al. 2019

Clin Experimental Allergy

Self Cite

View full text Add to dashboard Cite

Background There is growing evidence that environmental peanut exposure through non‐oral routes, including the skin and respiratory tract, can result in peanut sensitization. Environmental adjuvants in indoor dust can promote sensitization to inhaled antigens, but whether they contribute to peanut allergy development is unclear. Objective We investigated whether indoor dust promotes airway sensitization to peanut and peanut allergy development in mice. Methods Female and male C57BL/6J mice were exposed via the airways to peanut, indoor dust extract, or both for 2 weeks. Mice were then challenged with peanut and assessed for anaphylaxis. Peanut‐specific immunoglobulins, peanut uptake by lung conventional dendritic cells (cDCs), lung innate cytokines, and T cell differentiation in lung‐draining lymph nodes were quantified. Innate cytokine production by primary human bronchial epithelial cells exposed to indoor dust was also determined. Results Inhalational exposure to low levels of peanut in combination with indoor dust, but neither alone, resulted in production of peanut‐specific IgE and development of anaphylaxis upon peanut challenge. Indoor dust triggered production of innate cytokines in murine lungs and in primary human bronchial epithelial cells. Additionally, inhaled indoor dust stimulated maturation and migration of peanut‐laden lung type 1 cDCs to draining lymph nodes. Inhalational exposure to peanut and indoor dust induced peanut‐specific T helper 2 cell differentiation and accumulation of T follicular helper cells in draining lymph nodes, which were associated with increased B cell numbers and peanut‐specific immunoglobulin production. Conclusions & clinical relevance Indoor dust promotes airway sensitization to peanut and development of peanut allergy in mice. Our findings suggest that environmental adjuvants in indoor dust may be determinants of peanut allergy development in children.

show abstract

Epigenetic Control of Ccr7 Expression in Distinct Lineages of Lung Dendritic Cells

Cited by 26 publications

References 57 publications

microRNA-155 deficiency impairs dendritic cell function in breast cancer

microRNA-155 deficiency impairs dendritic cell function in breast cancer

Expression of Plet1 controls interstitial migration of murine small intestinal dendritic cells

Indoor dust acts as an adjuvant to promote sensitization to peanut through the airway

Contact Info

Product

Resources

About