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Imbalance of dendritic cell co-stimulation in COPD.

Stoll P, Ulrich M, Bratke K, Garbe K, Virchow JC, Lommatzsch M - Respir. Res. (2015)

Bottom Line: Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups.In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs.These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen).

View Article: PubMed Central - PubMed

Affiliation: Abteilung für Pneumologie und Internistische Intensivmedizin, Zentrum für Innere Medizin, Universität Rostock, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany. dr.paul.stoll@googlemail.com.

ABSTRACT

Background: Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.

Methods: Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.

Results: Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.

Conclusion: An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.

No MeSH data available.


Related in: MedlinePlus

Expression of PD-L1 and OX40L on blood DCs. Upper panel: expression (% positive blood DCs) of OX40L on blood mDCs (A) and PD-L1 on blood pDCs (B) of 21 never-smokers (Never-Smoker), 21 current smokers with normal lung function (Smoker) and 54 patients with COPD (COPD). Lowe panel: expression (% positive blood DCs) of OX40L on blood mDCs (C) and PD-L1 on blood pDCs (D) in those 27 COPD patients with less than 2 elevated markers of systemic inflammation (no systemic inflammation) and those 27 COPD patients with at least 2 elevated markers of systemic inflammation (systemic inflammation).
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Fig4: Expression of PD-L1 and OX40L on blood DCs. Upper panel: expression (% positive blood DCs) of OX40L on blood mDCs (A) and PD-L1 on blood pDCs (B) of 21 never-smokers (Never-Smoker), 21 current smokers with normal lung function (Smoker) and 54 patients with COPD (COPD). Lowe panel: expression (% positive blood DCs) of OX40L on blood mDCs (C) and PD-L1 on blood pDCs (D) in those 27 COPD patients with less than 2 elevated markers of systemic inflammation (no systemic inflammation) and those 27 COPD patients with at least 2 elevated markers of systemic inflammation (systemic inflammation).

Mentions: Patients with COPD displayed a significantly increased expression of BDCA-1 (Figure 3A), BDCA-3 (Figure 3B), CD86 (Figure 3C) and CCR5 (Figure 3D) on mDCs, as compared with never-smoking controls. However, the expression of these markers did not differ between asymptomatic smokers and patients with COPD (Table 3). There were no differences in the expression of CD54 and PD-L1 on mDCs between the groups (Table 3). The expression of OX40-ligand (OX40L) on mDCs was significantly higher in patients with COPD than in both control groups (Table 3 and Figure 4A). In contrast, the expression of PD-L1 on pDCs was significantly lower in patients with COPD, as compared with both control groups (Table 3 and Figure 4B). Consequently, the ratio of OX40L expression on mDCs to PD-L1 expression on pDCs (OX40L/PD-L1 ratio) was significantly increased in patients with COPD, as compared with both control groups (Figure 5A). There was no significant correlation between blood Tregs (total concentrations and percentages among CD4-positive T-cells) and the OX40L expression on mDCs, PD-L1 expression on pDCs and the OX40L/PD-L1 ratio (data not shown). CD54 expression on pDCs was significantly lower in patients with COPD than in asymptomatic smokers, but did not differ between patients with COPD and never-smoking controls (Table 3).Figure 3


Imbalance of dendritic cell co-stimulation in COPD.

Stoll P, Ulrich M, Bratke K, Garbe K, Virchow JC, Lommatzsch M - Respir. Res. (2015)

Expression of PD-L1 and OX40L on blood DCs. Upper panel: expression (% positive blood DCs) of OX40L on blood mDCs (A) and PD-L1 on blood pDCs (B) of 21 never-smokers (Never-Smoker), 21 current smokers with normal lung function (Smoker) and 54 patients with COPD (COPD). Lowe panel: expression (% positive blood DCs) of OX40L on blood mDCs (C) and PD-L1 on blood pDCs (D) in those 27 COPD patients with less than 2 elevated markers of systemic inflammation (no systemic inflammation) and those 27 COPD patients with at least 2 elevated markers of systemic inflammation (systemic inflammation).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4335663&req=5

Fig4: Expression of PD-L1 and OX40L on blood DCs. Upper panel: expression (% positive blood DCs) of OX40L on blood mDCs (A) and PD-L1 on blood pDCs (B) of 21 never-smokers (Never-Smoker), 21 current smokers with normal lung function (Smoker) and 54 patients with COPD (COPD). Lowe panel: expression (% positive blood DCs) of OX40L on blood mDCs (C) and PD-L1 on blood pDCs (D) in those 27 COPD patients with less than 2 elevated markers of systemic inflammation (no systemic inflammation) and those 27 COPD patients with at least 2 elevated markers of systemic inflammation (systemic inflammation).
Mentions: Patients with COPD displayed a significantly increased expression of BDCA-1 (Figure 3A), BDCA-3 (Figure 3B), CD86 (Figure 3C) and CCR5 (Figure 3D) on mDCs, as compared with never-smoking controls. However, the expression of these markers did not differ between asymptomatic smokers and patients with COPD (Table 3). There were no differences in the expression of CD54 and PD-L1 on mDCs between the groups (Table 3). The expression of OX40-ligand (OX40L) on mDCs was significantly higher in patients with COPD than in both control groups (Table 3 and Figure 4A). In contrast, the expression of PD-L1 on pDCs was significantly lower in patients with COPD, as compared with both control groups (Table 3 and Figure 4B). Consequently, the ratio of OX40L expression on mDCs to PD-L1 expression on pDCs (OX40L/PD-L1 ratio) was significantly increased in patients with COPD, as compared with both control groups (Figure 5A). There was no significant correlation between blood Tregs (total concentrations and percentages among CD4-positive T-cells) and the OX40L expression on mDCs, PD-L1 expression on pDCs and the OX40L/PD-L1 ratio (data not shown). CD54 expression on pDCs was significantly lower in patients with COPD than in asymptomatic smokers, but did not differ between patients with COPD and never-smoking controls (Table 3).Figure 3

Bottom Line: Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups.In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs.These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen).

View Article: PubMed Central - PubMed

Affiliation: Abteilung für Pneumologie und Internistische Intensivmedizin, Zentrum für Innere Medizin, Universität Rostock, Ernst-Heydemann-Str. 6, 18057, Rostock, Germany. dr.paul.stoll@googlemail.com.

ABSTRACT

Background: Dendritic cells (DCs) control immunity and play a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). However, the expression of function-associated surface molecules on circulating DCs in COPD is unknown.

Methods: Four-colour flow cytometry was used to compare blood DC surface molecules of 54 patients with COPD (median age: 59 years; median FEV1: 38% predicted, median CAT score: 24) with two age-matched control groups with normal lung function: 21 current smokers and 21 never-smokers.

Results: Concentrations of plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) and the mDC/pDC ratio did not differ between the groups. The increased expression of BDCA-1, BDCA-3, CD86 and CCR5 on mDCs in patients with COPD did not significantly differ from smokers with normal lung function. In contrast, COPD was specifically characterised by a decreased expression of the anti-inflammatory co-stimulatory molecule PD-L1 on pDCs and an increased expression of the pro-inflammatory co-stimulatory molecule OX40 ligand (OX40L) on mDCs. These changes were not confined to patients with elevated systemic inflammation markers (leukocytes, c-reactive protein, interleukin-6, fibrinogen). The ratio of OX40L to PD-L1 expression (OX40L/PD-L1 ratio), a quantitative measure of imbalanced DC co-stimulation, correlated with the severity of pulmonary emphysema in patients with COPD.

Conclusion: An imbalance of DC co-stimulation might contribute to the pathogenesis of COPD.

No MeSH data available.


Related in: MedlinePlus