Plasmacytoid dendritic cells in pulmonary lymphoid follicles of patients with COPD

Abstract

Plasmacytoid dendritic cells (pDCs) are professional antigen-presenting cells with antiviral and tolerogenic capabilities. Viral infections and autoimmunity are proposed to be important mechanisms in the pathogenesis of chronic obstructive pulmonary disease (COPD).The study aimed to quantify blood dendritic cell antigen 2-positive pDCs in lungs of subjects with or without COPD by immunohistochemistry and flow cytometry, combined with the investigation of the influence of cigarette smoke extract (CSE) on the function of pDCs in vitro.pDCs were mainly located in lymphoid follicles, a finding compatible with their expression of lymphoid homing chemokine receptors CXCR3 and CXCR4. pDC accumulated in the lymphoid follicles and in lung digests of patients with mild to moderate COPD, compared with smokers without airflow limitation and patients with COPD Global Initiative for Chronic Obstructive Lung disease (GOLD) stage III-IV. Exposing maturing pDC of healthy subjects to CSE in vitro revealed an attenuation of the expression of co-stimulatory molecules and impaired interferon-a production. Maturing pDC from patients with COPD produced higher levels of tumour necrosis factor (TNF)-a and interleukin (IL)-8 compared to pDC from healthy subjects.CSE significantly impairs the antiviral function of pDCs. In COPD, a GOLD stage dependent accumulation of pDC in lymphoid follicles is present, combined with an enhanced production of TNF-a and IL-8 by maturing pDCs.

Differential switching to IgG and IgA in active smoking COPD patients and healthy controls

“…Furthermore, we demonstrated the presence of oligoclonal Bcells with ongoing mutation in these follicles [5], indicating the presence of a specific B-cell response. Several reports have now confirmed the presence of B-cell follicles in COPD [6][7][8][9][10], some also in relation to disease severity. Notably, POLVERINO et al [8] showed the presence of BAFF (B-cell-activating factor of the tumour necrosis factor family) in these follicles, which is a marker of B-cell survival and activation, and has been associated with autoimmune diseases [11,12].…”

“…Flow cytometry analysis 1610 6 PBMCs or lung leukocytes were stained with Alexa Fluor1 700-conjugated anti-CD20, allophycocyanin (APC)-and Cy7-conjugated anti-CD27, phycoerythrin (PE)-and Cy7-conjugated anti-CD38, APC-conjugated anti-CD138, biotinylated anti-IgM followed by PE-conjugated streptavidin (BD Biosciences, San Jose, CA, USA), PE-and Cy5-conjugated anti-IgG (eBioscience, Vienna, Austria), fluorescein isothiocyanate (FITC)-conjugated anti-CD3 (BD Bioscience), FITCconjugated anti-CD14 (IQ Products, Groningen, the Netherlands) and FITC-conjugated anti-CD16 (IQ Products). Fluorescent staining of the cells was measured on a LSR-II flow cytometer (BD Biosciences) and data were analysed using FlowJo software (Tree Star Inc., Ashland, OR, USA).…”

“…Next, the different B-cell subsets were distinguished based on the expression of CD20, CD27, IgM and IgG. Total B-cells were analysed based on CD20 expression, and total memory B-cells were analysed based on co-expression of CD20 and CD27 ( PBMC stimulation 2610 6 PBMCs from COPD patients and healthy controls were stimulated for 6 days with lung elastin, lung collagen (both 1 mg?mL ; eBioscience) (cytokine mix) to stimulate plasma cell differentiation and Ig production (referred to hereafter as extracellular matrix (ECM) plus cytokine mix stimulation). A double dose of this cytokine mix served as positive control (referred to hereafter as cytokine mix stimulation) and no stimulants as negative control.…”

Regulation of inducible BALT formation and contribution to immunity and pathology

“…More recently, plasmacytoid DCs were found to accumulate in the lymphoid follicles of COPD patients. 77 These were able to produce higher levels of TNFand IL-8 upon maturation as compared with plasmacytoid DCs from healthy subjects, but the role of these cells in iBALT formation and maintenance remains an open question.…”

Ectopic lymphoid follicles: inducible centres for generating antigen‐specific immune responses within tissues

“…Ectopic lymphoid follicles are associated with various autoimmune and chronic inflammatory diseases including rheumatoid arthritis,11, 101, 102 Sjögren syndrome,103 multiple sclerosis,104 experimental diabetes,105 atherosclerosis,106, 107 inflammatory bowel disease108, 109 and chronic obstructive pulmonary disease110, 111 (for a comprehensive review of ELFs in autoimmunity see refs 10, 76). In contrast to their roles in infection and cancer, ELFs in chronic inflammatory diseases are primarily associated with disease exacerbation.…”