Increased Transplant Arteriosclerosis in the Absence of CCR7 is Associated With Reduced Expression of Foxp3

Ensminger, Stephan; Helm, S; Ohl, Lars; Spriewald, Bernd M.; Abele, S.; Wollin, M.; Wood, Kathryn J.; Weyand, Michael; Förster, Reinhold

doi:10.1097/tp.0b013e3181826a97

Cited by 7 publications

(6 citation statements)

References 48 publications

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“…The use of animal models has also demonstrated that periodontal symptoms upon P. gingivalis infection are worsened with diabetes (Ensminger et al, 2008), but the mechanisms are unclear. Further, TLR-2 activation and signaling, which are pronounced during CP and which are crucial for mDC function against P. gingivalis (Asai et al, 2007; Kanaya et al, 2009), have been found to play a role in autoimmune diabetes progression (Kim et al, 2011; Lee et al, 2011).…”

Section: A Role For MDC Fluctuation and Inflammatory Response In Diabmentioning

confidence: 99%

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

et al. 2014

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The majority of risk factors for chronic inflammatory diseases are unknown. This makes personalized medicine for assessment, prognosis, and choice of therapy very difficult. It is becoming increasingly clear, however, that low-grade subclinical infections may be an underlying cause of many chronic inflammatory diseases and thus may contribute to secondary outcomes (e.g., cancer). Many diseases are now categorized as inflammatory-mediated diseases that stem from a dysregulation in host immunity. There is a growing need to study the links between low-grade infections, the immune responses they elicit, and how this impacts overall health. One such link explored in detail here is the extreme sensitivity of myeloid dendritic cells (mDCs) in peripheral blood to chronic low-grade infections and the role that these mDCs play in arbitrating the resulting immune responses. We find that emerging evidence supports a role for pathogen-induced mDCs in chronic inflammation leading to increased risk of secondary clinical disease. The mDCs that are elevated in the blood as a result of low-grade bacteremia often do not trigger a productive immune response, but can disseminate the pathogen throughout the host. This aberrant trafficking of mDCs can accelerate systemic inflammatory disease progression. Conversely, restoration of dendritic cell homeostasis may aid in pathogen elimination and minimize dissemination. Thus it would seem prudent when assessing chronic inflammatory disease risk to consider blood mDC numbers, and the microbial content (microbiome) and activation state of these mDCs. These may provide important clues (“the canary in the coal mine”) of high inflammatory disease risk. This will facilitate development of novel immunotherapies to eliminate such smoldering infections in atherosclerosis, cancer, rheumatoid arthritis, and pre-eclampsia.

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Section: A Role For MDC Fluctuation and Inflammatory Response In Diabmentioning

confidence: 99%

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

et al. 2014

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“…As CCR7 is essential for migration of DC to lymph nodes, it is not unexpected that CCR7 surface levels increase during inflammatory conditions (7). Indeed, CCR7 overexpression causes immature DC to migrate to DLN (8), and CCR7 2/2 mice contain mDC that fail to migrate and are incapable of promoting adaptive immune responses (7,9). Migrating DC, under specific conditions, also hold the capacity to mediate T regulatory (Treg) cell differentiation and facilitate Ag-specific immune tolerance.…”

Section: Endritic Cells (Dc) Undergo Transition From Immature DCmentioning

confidence: 99%

“…Migrating DC, under specific conditions, also hold the capacity to mediate T regulatory (Treg) cell differentiation and facilitate Ag-specific immune tolerance. Indeed, CCR7 2/2 mice exhibit reduced numbers of protective CD4 + CD25 + Foxp3-positive Treg cells (9), and human DC deficiencies exhibit a sharp loss in Treg cell numbers (10).…”

Section: Endritic Cells (Dc) Undergo Transition From Immature DCmentioning

confidence: 99%

α-1 Antitrypsin Promotes Semimature, IL-10–Producing and Readily Migrating Tolerogenic Dendritic Cells

Ozeri

Mizrahi

Shahaf

et al. 2012

The Journal of Immunology

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Tolerogenic IL-10–positive CCR7-positive dendritic cells (DC) promote T regulatory (Treg) cell differentiation upon CCR7-dependent migration to draining lymph nodes (DLN). Indeed, in human DC deficiencies, Treg levels are low. α-1 antitrypsin (AAT) has been shown to reduce inflammatory markers, promote a semimature LPS-induced DC phenotype, facilitate Treg expansion, and protect pancreatic islets from alloimmune and autoimmune responses in mice. However, the mechanism behind these activities of AAT is poorly understood. In this study, we examine interactions among DC, CD4+ T cells, and AAT in vitro and in vivo. IL-1β/IFN-γ–mediated DC maturation and effect on Treg development were examined using OT-II cells and human AAT (0.5 mg/ml). CCL19/21-dependent migration of isolated DC and resident islet DC was assessed, and CCR7 surface levels were examined. Migration toward DLN was evaluated by FITC skin painting, transgenic GFP skin tissue grafting, and footpad DC injection. AAT-treated stimulated DC displayed reduced MHC class II, CD40, CD86, and IL-6, but produced more IL-10 and maintained inducible CCR7. Upon exposure of CD4+ T cells to OVA-loaded AAT-treated DC, 2.7-fold more Foxp3+ Treg cells were obtained. AAT-treated cells displayed enhanced chemokine-dependent migration and low surface CD40. Under AAT treatment (60 mg/kg), DLN contained twice more fluorescence after FITC skin painting and twice more donor DC after footpad injection, whereas migrating DC expressed less CD40, MHC class II, and CD86. Intracellular DC IL-10 was 2-fold higher in the AAT group. Taken together, these results suggest that inducible functional CCR7 is maintained during AAT-mediated anti-inflammatory conditions. Further studies are required to elucidate the mechanism behind the favorable tolerogenic activities of AAT.

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“…CCR7 has been reported to mediate regulatory CD4 ϩ FoxP3 ϩ T-cell infiltration. 34 The mRNA expression of IL-10 and TGF-␤ was also increased at 3 and 10 days, implying Treg activity and inhibition of Th1 response. 35 Due to the lack of alloantigens, inflammation subsided and the syngrafts showed normal respiratory epithelium and no tracheal occlusion at 30 days.…”

Section: Discussionmentioning

confidence: 97%

Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts

Ropponen

Syrjälä

Krebs

et al. 2011

The Journal of Heart and Lung Transplantation

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Increased Transplant Arteriosclerosis in the Absence of CCR7 is Associated With Reduced Expression of Foxp3

Cited by 7 publications

References 48 publications

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

Blood dendritic cells: “canary in the coal mine” to predict chronic inflammatory disease?

α-1 Antitrypsin Promotes Semimature, IL-10–Producing and Readily Migrating Tolerogenic Dendritic Cells

Innate and adaptive immune responses in obliterative airway disease in rat tracheal allografts

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