Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

Pottelberge, Geert R. Van; Bracke, Ken R.; Demedts, Ingel K.; Rijck, Kim De; Reinartz, Susanne M.; Drunen, Cornelis M. van; Verleden, Geert M.; Vermassen, Frank; Joos, Guy; Brusselle, Guy

doi:10.1186/1465-9921-11-35

Cited by 78 publications

(52 citation statements)

References 50 publications

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“…This remarkably poor polymorphism, which was confirmed by sequencing exons 2 and 3 of the HLA-DQA2 and -DQB2 genes in a panel of HLA-DR, DQA1, DQB1 and DPA1 homozygous IHW cell lines, is reminiscent of the CD1 molecule system; it suggests that HLA-DQa2/b2 antigenic ligands share conserved biochemical or biophysical properties, which would make their characterization crucial. It is worth noting that LCs are also present in oral and genital mucosae, and cells expressing Langerin have been described in the human lung (30), liver (31) and cornea (32). Determining whether the HLA-DQA2 and -DQB2 genes are likewise expressed in such Langerin-positive DCs residing in tissues outside the skin might provide a clue as to the function of HLA-DQa2/b2 molecules and why their expression appears to be confined to LCs.…”

Section: Discussionmentioning

confidence: 99%

HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule

Lenormand

Bausinger

Gross

et al. 2012

The Journal of Immunology

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The precise role of human epidermal Langerhans cells (LCs) in immune response is highly controversial. While studying the gene expression profile of these cells, we were intrigued to identify the HLA-DQB2 gene as potentially expressed in LCs. Despite a strong evolutionary conservation of their sequences, the concomitant expression of the poorly polymorphic HLA-DQA2/HLA-DQB2 genes, paralogous to the HLA-DQA1/HLA-DQB1 genes, has never been detected in any cell type. We confirmed by RT-PCR that the HLA-DQA2 and -DQB2 genes are both expressed in LCs, but not in monocyte-derived dendritic cells, or in blood CD1c+ or plasmacytoid dendritic cells. The presence of the HLA-DQβ2 chain in LCs could be demonstrated by Western blotting, whereas immunofluorescence revealed its localization in early endosomes. As in the case of other HLA class II molecules, the HLA-DQα2 and -DQβ2 chains formed heterodimers that had to associate with the invariant chain to reach endosomal compartments. HLA-DQα2/β2 heterodimers were expressed at the cell surface, where they could mediate staphylococcal superantigen stimulation of T cells. Interestingly, HLA-DQα2 and HLA-DQβ1 chains formed mixed heterodimers which efficiently left the endoplasmic reticulum. These observations strongly suggest that the poorly polymorphic HLA-DQA2 and -DQB2 genes should be considered to be of immunological importance. The HLA-DQα2/β2 molecules could influence the complexity of the repertoire of Ags presented by LCs.

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Section: Discussionmentioning

confidence: 99%

HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule

Lenormand

Bausinger

Gross

et al. 2012

The Journal of Immunology

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“…Paraffin-embedded sections of human lung tissue were subjected to activin-A staining using anti-activin-A antibody as previously described [21]. Immunohistochemical staining with anti-activin-A (R&D Systems, Abingdon, UK) was performed on paraffin sections of the left lung of mice.…”

Section: Activin-a Immunohistochemistry and Quantificationmentioning

confidence: 99%

Role of activin-A in cigarette smoke-induced inflammation and COPD

Verhamme

Bracke²,

Amatngalim³

et al. 2013

Eur Respir J

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Activin-A is a pleiotropic cytokine belonging to the transforming growth factor-b superfamily and has been implicated in asthma and pulmonary fibrosis. However, the role of activin-A and its endogenous inhibitor, follistatin, in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unknown.We first quantified activin-A and follistatin in the lungs of air-or cigarette smoke-exposed mice and in the lungs of patients with COPD by immunohistochemistry, ELISA and quantitative real-time PCR. We subsequently studied the effect of cigarette smoke on primary human bronchial epithelial cells in vitro. Next, activin-A signalling was antagonised in vivo by administration of follistatin in mice exposed to air or cigarette smoke for 4 weeks.Protein levels of activin-A were increased in the airway epithelium of patients with COPD compared with never-smokers and smokers. Cigarette smoke-exposed human bronchial epithelial cells expressed higher levels of activin-A and lower levels of follistatin. Both mRNA and protein levels of activin-A were increased in the lungs of cigarette smoke-exposed mice, whereas follistatin levels were reduced upon cigarette smoke exposure. Importantly, administration of follistatin attenuated the cigarette smoke-induced increase of inflammatory cells and mediators in the bronchoalveolar lavage fluid in mice.These results suggest that an imbalance between activin-A and follistatin contributes to the pathogenesis of cigarette smoke-induced inflammation and COPD. @ERSpublications Imbalance of activin-A and FST in favour of activin-A signalling in COPD patients cigarette smokeexposed mice http://ow.ly/qMqVN For editorial comments see page 954.

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“…Conversely, a significant increase of langerin-expressing (CD207)+ DCs has been observed in the small airways of patients with COPD and was associated with upregulation of CCL20 [6,27,28], the most potent chemokine in attracting DCs. Moreover, the number of langerin+ DCs infiltrating the small airways increased progressively along with increasing severity of the disease, a finding that we confirmed in our study in bronchial biopsies.…”

Section: Discussionmentioning

confidence: 99%

Decreased Maturation of Dendritic Cells in the Central Airways of COPD Patients Is Associated with VEGF, TGF-β and Vascularity

et al. 2014

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Background: Dendritic cells (DCs) have a pivotal role in the onset and regulation of innate and adaptive immune responses. Moreover, DCs can interact with angiogenic modulators, resulting in modification of their biology and participation in angiogenesis. Objectives: This study was designed to evaluate the relationship between the density of DCs, vascularity and expression of angiogenic factors [vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β and basic fibroblast growth factor (bFGF)] in the central airways of chronic obstructive pulmonary disease (COPD) patients. Methods: The study included 20 patients with moderate/severe COPD and 8 healthy control subjects. Bronchial biopsies were evaluated by immunohistochemistry. Specimens were examined for CD83 and CD207 to mark mature and immature DCs, respectively, for collagen IV to evaluate vascularity, and for VEGF, TGF-β and bFGF. Results: Compared to controls, COPD patients had a significant reduction of CD83+ cells and an increased CD207/CD83 ratio (p < 0.05). Vascularity, VEGF, TGF-β and bFGF were also significantly increased in COPD patients as compared to controls (p < 0.01). In COPD patients, CD83+ cells were inversely related to VEGF and TGF-β expression (p < 0.05). Moreover, the CD207/CD83 ratio was positively related to VEGF, TGF-β and vascularity (p < 0.05). Finally, CD207+ cells were inversely related to FEV₁ (p < 0.05). Conclusion: Our results show a reduced maturation of DCs in COPD that was related to airway vascularity and angiogenic factors (VEGF and TGF-β). Additionally, immature DCs were significantly related to disease severity. We propose that the interplay between airway vascular changes, on one hand, and DCs maturation on the other, may play a key role in the pathogenetic mechanisms of COPD.

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Selective accumulation of langerhans-type dendritic cells in small airways of patients with COPD

Cited by 78 publications

References 50 publications

HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule

HLA-DQA2 and HLA-DQB2 Genes Are Specifically Expressed in Human Langerhans Cells and Encode a New HLA Class II Molecule

Role of activin-A in cigarette smoke-induced inflammation and COPD

Decreased Maturation of Dendritic Cells in the Central Airways of COPD Patients Is Associated with VEGF, TGF-β and Vascularity

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