Airway dendritic cell phenotypes in inflammatory diseases of the human lung

Abstract

Airway dendritic cells (DCs) are key regulators of pulmonary immune responses. However, information is limited regarding the characteristics of airway DCs in human lung diseases.Plasmacytoid DCs (pDCs) and myeloid DCs (mDCs) were analysed using four-colour flow cytometry in bronchoalveolar lavage fluid (BALF) from nonsmoking controls and patients with sarcoidosis, idiopathic pulmonary fibrosis (IPF) and pneumonia (in the presence or absence of immunosuppression).Compared with controls, immunocompetent patients with pneumonia displayed strongly enhanced pDC counts in BALF. In contrast, pDC counts in BALF from immunocompromised patients with pneumonia were even lower than in controls. This discrepancy was not explained by a different chemotactic milieu in the airways; all patients with pneumonia were characterised by strongly increased concentrations of the pDC-attracting chemokine, CXC chemokine ligand 10, in BALF. Patients with IPF were characterised by normal percentages of DC subtypes. However, the mDCs of patients with IPF were not as mature (CD83-positive) as those of controls. Patients with sarcoidosis displayed a unique increase in CD1a-negative mDCs in the airways. In addition, there was altered expression of costimulatory molecules (increased CD80 and decreased CD86 expression) on mDCs in patients with sarcoidosis.These data suggest that inflammatory diseases of the human lung are associated with a differential phenotype and recruitment of airway dendritic cells.

Effect of Prostaglandin I2 Analogs on Cytokine Expression in Human Myeloid Dendritic Cells via Epigenetic Regulation

“…As shown in Figure 7, iloprost downregulated poly I:C-induced H3K4 trimethylation in the TNFA gene promoter region from upstream to downstream of the transcription start site ( Figure 7A). Be- cause histone trimethylation is mediated by methyltransferase, we next examine whether the downregulation of H3K4 trimethylation by iloprost is associated with the downregulation of the H3K4-specific methyltransferases and MLL and WDR5 proteins (9). Intriguingly, poly I:C-induced translocation of MLL and WDR5 protein from cytoplasm into nucleus, and iloprost, can partly reversed the translocation of MLL and WDR5 proteins from cytoplasm to nucleus by poly I:C (Figures 7B, D).…”

“…DCs play a major role in initiation and regulation of adaptive immune responses to the stimulation of antigens and allergens (9). In a murine asthma model, myeloid dendritic cells (mDCs) accumulate in the allergen-challenged airways during the acute phase, and the depletion of mDCs attenuates the airway inflammation and hyperresponsiveness (10).…”

Dendritic Cells and Monocytes with Distinct Inflammatory Responses Reside in Lung Mucosa of Healthy Humans

“…In studies applying more advanced flow cytometry panels, noncancerous lung tissue from surgical resections of patients were typically used (14,(26)(27)(28), although it is unclear whether these rare populations are truly representative of DCs present in healthy subjects. Indeed, several studies have investigated DCs in the context of lung diseases such as asthma, chronic obstructive pulmonary disease, bronchiolitis, and sarcoidosis (29)(30)(31)(32)(33)(34)(35). In chronic obstructive pulmonary disease, the expression of maturation molecules on DCs has been proposed as a potential diagnostic/therapeutic target.…”

Cellular Defences of the Lung: Comparative Perspectives

“…Havenith et al, 1993;Xia et al, 1995): within 12 hours, the lung derived DCs can be found in the T-cell area of draining mediastinal lymph nodes of the lung. Inflammatory diseases of the human lung are associated with the different phenotypes and the process of the recruitment of the airway DCs (Lommatzsch et al, 2007(Lommatzsch et al, , 2010Geurtsvankessel and Lambrecht, 2008;Vassallo et al, 2010). Regulation of galectin-3 in the lungs may represent one of the multiple potential mechanisms by which galectins contribute to modulation of the innate and acquired immune responses (Maldonado et al, 2011).…”

“…Highly specialized and notably heterogenous, DCs function as messengers and regulators between innate and acquired immunity (e.g. Reid, 1997;Hart, 1997;Banchereau and Steinman, 1998;Austyn, 1998;Satthaporn and Eremin, 2001;Dzionek et al, 2000;Webb et al, 2005;McKenna et al, 2005;Lommatzsch et al, 2007Lommatzsch et al, , 2010GeurtsvanKessel and Lambrecht, 2008;von Garnier and Nicod, 2009). Because DCs have the ability to induce a primary immune response in resting naïve T-lymphocytes and play a role in the maintenance of B-cell function and antigen memory (recall) responses (e.g.…”