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

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

doi:10.1186/1465-9921-11-35

Geert R Van Pottelberge, Frank E Vermassen + Show 8 more

Open Access

https://doi.org/10.1186/1465-9921-11-35

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Abstract

BackgroundDendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and ex-smokers with or without COPD.MethodsMyeloid DC were characterized using flowcytometry on single cell suspensions of digested human lung tissue. Immunohistochemical staining for langerin, BDCA-1, CD1a and DC-SIGN was performed on surgical resection specimens from 85 patients. Expression of factors inducing Langerhans-type DC (LDC) differentiation was evaluated by RT-PCR on total lung RNA.ResultsTwo segregated subsets of tissue resident pulmonary myeloid DC were identified in single cell suspensions by flowcytometry: the langerin+ LDC and the DC-SIGN+ interstitial-type DC (intDC). LDC partially expressed the markers CD1a and BDCA-1, which are also present on their known blood precursors. In contrast, intDC did not express langerin, CD1a or BDCA-1, but were more closely related to monocytes.Quantification of DC in the small airways by immunohistochemistry revealed a higher number of LDC in current smokers without COPD and in COPD patients compared to never smokers and ex-smokers without COPD. Importantly, there was no difference in the number of LDC between current and ex-smoking COPD patients.In contrast, the number of intDC did not differ between study groups. Interestingly, the number of BDCA-1+ DC was significantly lower in COPD patients compared to never smokers and further decreased with the severity of the disease. In addition, the accumulation of LDC in the small airways significantly correlated with the expression of the LDC inducing differentiation factor activin-A.ConclusionsMyeloid DC differentiation is altered in small airways of current smokers and COPD patients resulting in a selective accumulation of the LDC subset which correlates with the pulmonary expression of the LDC-inducing differentiation factor activin-A. This study identified the LDC subset as an interesting focus for future research in COPD pathogenesis.

Highlights

Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in Chronic Obstructive Pulmonary Disease (COPD) pathogenesis remain to be elucidated
Characterization of pulmonary Langerhans-type and interstitial-type DC Figure 1 shows the flowcytometric identification of langerin (CD207)+ Langerhans-type DC (LDC) and DC-SIGN (CD209)+ intDC in single cell suspensions of digested human lung tissue, using the previously described low autofluorescent, CD3 negative, CD19 negative gating strategy [13]
CD1a, present on a subset of pulmonary BDCA-1+ DCs, is present on a subgroup of LDC, but not all LDC co-express CD1a, suggesting that CD1a is not a good surrogate marker for pulmonary LDC. This finding is supported by the distribution of CD1a in the small airways of human lungs which is completely different from langerin and BDCA-1 as CD1a positive cells are mainly present in the lamina propria and the adventitia

Summary

Introduction

Dendritic cells (DC) linking innate and adaptive immune responses are present in human lungs, but the characterization of different subsets and their role in COPD pathogenesis remain to be elucidated. The aim of this study is to characterize and quantify pulmonary myeloid DC subsets in small airways of current and exsmokers with or without COPD. Several studies identified the important role of the activated innate immune response in the pathogenesis of COPD, with neutrophils and macrophages as major effector cells, inducing tissue destruction by proteolysis and oxidative stress [4,5,6]. Other studies addressed the role of the adaptive immune response in COPD, with increased numbers of lymphoid follicles and the presence of cytotoxic CD8+ T cells and B cells, reflecting a sustained immune response, even after smoking cessation [7,8,9,10]

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