Imbalance of dendritic cell co-stimulation in COPD

Stoll, Paul; Ulrich, Martin; Bratke, Kai; Garbe, Katharina; Virchow, J. Christian; Lommatzsch, Marek

doi:10.1186/s12931-015-0174-x

Cited by 28 publications

(31 citation statements)

References 37 publications

(47 reference statements)

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“…pDCs are the largest producers of interferon-α which can augment the anti-viral response in COPD, while mDC provides a major source of T-cell stimuli and inflammatory cytokines. The reduction in mDC:pDC ratio by MSC infusion may have direct benefits in COPD since an increased ratio of mDC:pDC subsets has been associated with higher grade emphysematous damage in COPD patients [14]. Furthermore, CD14 + monocytes were significantly increased at day 2 (figure 1k).…”

mentioning

confidence: 98%

Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study

et al. 2018

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Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study To the Editor: Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality due to limited therapeutic options for the persistent pulmonary and systemic inflammation that characterises this condition [1]. Recently, pre-clinical studies of mesenchymal stromal cells (MSCs) in COPD demonstrate efficacy in alleviating inflammation and reducing emphysema following either systemic or intra-tracheal administration [2, 3]. Human trials have demonstrated that MSCs did not improve spirometry following their administration to COPD patients; however, it was reported that C-reactive protein (CRP), a marker for systemic inflammation, was reduced 1-3 months after infusion. Earlier time-points were not assessed in detail in these trials, which limits further investigation of these changes [4, 5]. Identifying the fate of intravenously infused MSCs and the potential implications of their biodistribution, as well as short-term MSC-induced systemic changes that were not explored in previous trials will better delineate the utility of MSC treatment for COPD. The study was approved by the Royal Perth Hospital ethics committee (approval number EC2012/103) and all patients had provided written informed consent. A single site, phase I study (Australian clinical trials registry number 12614000731695) was conducted to determine MSC biodistribution, inflammatory and clinical endpoints following systemic MSC infusion in a cohort (n=9) of mild to very severe stable COPD patients (n=1 Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I, n=2 GOLD II, n=3 GOLD III, n=3 GOLD IV). All recruited patients had not experienced an exacerbation for at least 3 months prior to trial commencement with no change in regular medications. Patients received two infusions of low passage (p4-5) allogeneic bone marrow-derived MSCs of approximately 2×10 6 MSCs per kg, 1 week apart, with the first infusion comprising radiolabelled cells and the second infusion using unlabelled cells. MSCs used for the first infusion were labelled with indium-111, a low energy radioisotope with a half-life of 68 h to enable tracking across several days. Labelled MSCs were able to adequately suppress peripheral blood mononuclear cell (PBMC) proliferation in vitro compared to unlabelled MSC (p>0.05) and retained regular morphological characteristics. Safety and hospitalisations attributed to acute exacerbations of COPD were monitored up to 1 year later. Wilcoxon matched pairs tests were used for comparison of pre-and post-infusion levels of cell subsets and circulating plasma biomarkers. MSC infusion showed no attributable adverse side-effects and was well tolerated. Following infusion, indium-111 was detected in the lung within 30 min by computed tomography (CT) scan and remained detectable after 24 h, after which uptake was detected in the liver, spleen and bone marrow up to 7 days after infusion (figure 1a ...

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confidence: 98%

Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study

et al. 2018

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“…We thank Dr Stoll and colleagues for highlighting the clinically important issues raised by the recent work on the PD1 axis in COPD (1,2). In light of these findings we share their concern that the use of anti-PD-1-PD-L1 therapies in patients with non-small cell lung cancer (NSCLC) and COPD may have unwanted effects on the underlying airway inflammatory process.…”

Section: To the Editormentioning

confidence: 90%

Reply: The PD-1–PD-L1 Axis in Chronic Obstructive Pulmonary Disease

Staples

Wilkinson

2016

Am J Respir Crit Care Med

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“…Dendritic cells (DCs) are antigen-presenting, playing a critical role in linking the innate to the adaptive immune response [24]. Immature dendritic cells (DC0) near the epithelial surface are activated directly by BS or dangerous signals generated from TD [1,11].…”

Section: A Network Modelmentioning

confidence: 99%

Network modeling of inflammatory dynamics induced by biomass smoke leading to chronic obstructive pulmonary disease

Pan

Liao

2018

Chinese Journal of Chemical Physics

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Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disorder characterized by airflow obstruction and progressive damage of lung tissues. As currently more than 3 billion people use biomass fuel for cooking and heating worldwide, exposure to biomass smoke (BS) is recognized as a significant risk factor for COPD. Recent clinical data have shown that BS-COPD patients have a Th2-type inflammatory profile significantly different from that in COPD induced by cigarette smoke. As COPD is essentially proinflammatory, however, the mechanism underlying this Th2-type anti-inflammatory profile remains elusive. In this work, a network model is applied to study BS-induced inflammatory dynamics. The network model involves several positive feedback loops, activations of which are responsible for different mechanisms by which clinical phenotypes of COPD are produced. Our modeling study in this work has identified a subset of BS-COPD patients with a mixed M1-and Th2-type inflammatory profile. The model's prediction is in good agreement with clinical experiments and our in silico knockout simulations have demonstrated several important network components that play an important role in the disease. Our modeling study provides novel insight into BS-COPD progression, offering a rationale for targeted therapy and personalized medicine for treatment of the disease in future.

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Imbalance of dendritic cell co-stimulation in COPD

Cited by 28 publications

References 37 publications

Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study

Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study

Reply: The PD-1–PD-L1 Axis in Chronic Obstructive Pulmonary Disease

Network modeling of inflammatory dynamics induced by biomass smoke leading to chronic obstructive pulmonary disease

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