The role of dendritic cells in asthma

Gill, Michelle A.

doi:10.1016/j.jaci.2012.02.028

Cited by 109 publications

(99 citation statements)

References 114 publications

(131 reference statements)

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“…Among those, the DC is the most powerful APC, contributing to primary and secondary immune responses, including allergic immunity. Mature DCs (mDCs) with high levels of expression of the co-stimulatory molecules CD80 and CD86 can activate T cells, while immature dendritic cells (iDCs) with a low level of expression of CD80 and CD86 suppress the T-cell response and induce immune tolerance (20,21). DCs in patients with asthma have been demonstrated to be hyperactive (22).…”

Section: Discussionmentioning

confidence: 99%

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Yan

et al. 2016

Experimental and Therapeutic Medicine

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Abstract. Dendritic cells (DCs) are associated with the activation and differentiation of T helper (Th) cells. Cluster of differentiation (CD)80 and CD86, the co-stimulatory molecules highly expressed in DCs, have are prominent in promoting the differentiation of Th cells toward Th2 cells. However, little is known about the effect of CD80 and CD86 knockdown on Th1/Th2 cytokine production in mature DCs (mDCs). The aim of the present study was to investigate whether small-interfering RNA (siRNA) could suppress the surface expression of CD80 and CD86 in mDCs. The effects of CD80 and CD86 knockdown in mDCs on Th1/Th2 cytokine expression were examined using an asthmatic murine model. DCs were isolated, separated and cultured in vitro. Flow cytometry was used to examine the expression of CD11c, CD80 and CD86 on the DCs. The DCs were transfected with CD80-and CD86-specific siRNA, while non-siRNA and negative siRNA controls were also designed. Then, the mRNA and protein expression levels of CD80 and CD86 were determined by reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. The levels of interferon (IFN)-γ and interleukin (IL)-4 produced by T cells co-cultured with mDCs were measured by enzyme-linked immunosorbent assay. Substantial downregulation of CD80 and CD86 mRNA and protein levels were observed in the mDCs following transfection with siRNA. The level of IFN-γ produced by T cells co-cultured with mDCs was significantly increased in the siRNA group, while IL-4 production was significantly decreased. These results show that specific targeting of CD80 and CD86 with siRNA is able to suppress CD80/CD86 expression and consequently regulate Th1/Th2 cytokine levels by increasing IFN-γ production and decreasing IL-4 levels in an asthmatic murine model.

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Section: Discussionmentioning

confidence: 99%

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Yan

et al. 2016

Experimental and Therapeutic Medicine

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“…Emerging evidence suggests an ever-more important role for dendritic cells in the immune response to environmental allergens (45)(46)(47). Many of the cell types involved in asthma pathogenesis, including eosinophils, neutrophils, and T cells, are normally capable of producing ROS.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of gp91phox Inhibits Allergic Airway Inflammation

Sevin

Newcomb

Toki

et al. 2013

Am J Respir Cell Mol Biol

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Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a multienzyme complex, is the major source for production of reactive oxygen species (ROS). ROS are increased in allergic diseases, such as asthma, but the role of ROS in disease pathogenesis remains uncertain. We hypothesized that mice unable to generate ROS via the NADPH oxidase pathway would have decreased allergic airway inflammation. To test this hypothesis, we studied gp91phox 2/2 mice in a model of allergic airway inflammation after sensitization and challenge with ovalbumin. Serum, bronchoalveolar lavage fluid, and lungs were then examined for evidence of allergic inflammation. We found that mice lacking a functional NADPH oxidase complex had significantly decreased ROS production and allergic airway inflammation, compared with wild-type (WT) control animals. To determine the mechanism by which allergic inflammation was inhibited by gp91phox deficiency, we cultured bone marrowderived dendritic cells from WT and gp91phox 2/2 mice and activated them with LPS. IL-12 expression was significantly increased in the gp91phox 2/2 bone marrow-derived dendritic cells, suggesting that the cytokine profile produced in the absence of gp91phox enhanced the conditions leading to T helper (Th) type 1 differentiation, while inhibiting Th2 polarization. Splenocytes from sensitized gp91phox 2/2 animals produced significantly less IL-13 in response to ovalbumin challenge in vitro compared with splenocytes from sensitized WT mice, suggesting that NADPH oxidase promotes allergic sensitization. In contrast, inflammatory cytokines produced by T cells cultured from WT and gp91phox 2/2 mice under Th0, Th1, Th2, and Th17 conditions were not significantly different. This study demonstrates the importance of NADPH oxidase activity and ROS production in a murine model of asthma.Keywords: asthma; allergic airway inflammation; gp91phox; reactive oxygen species; NADPH oxidase Asthma is a significant health problem, affecting up to 300 million children and adults around the world (1). In the United States alone, costs associated with asthma exceed $50 billion each year due to health care use and lost productivity (2). The prevalence of this disease is increasing, without clear etiology (3, 4). Chronic inflammation of the airways is a hallmark of the disease (5), and yet, despite widespread research, the mechanisms of persistent allergic airway inflammation are poorly understood.Reactive oxygen species (ROS) are increased in allergic diseases, such as asthma, and ROS production is associated with airway inflammation and airway hyperresponsiveness (6). Breath condensates from subjects with asthma have been shown to contain increased hydrogen peroxide, an ROS, and 8-isoprostane, an F 2 -isoprostane that is a marker of oxidative stress, compared to control subjects without asthma (7-9). In addition, increased levels of peroxidation products are present in the serum, urine, and lung tissue of patients with asthma compared with those without asthma (10-12). Mice with allergic lung inf...

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“…1 DCs, and CD11b 1 DCs), play an important role in lung development and physiology, and contribute to important lung diseases, including pulmonary infection, cancer, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis (1)(2)(3)(4)(5). Alveolar and interstitial lung macrophages exhibit different origins and life spans in lungs, and have been identified as key regulators of pathological and reparative processes.…”

mentioning

confidence: 99%

Flow Cytometric Analysis of Macrophages and Dendritic Cell Subsets in the Mouse Lung

Misharin

Morales‐Nebreda

Mutlu

et al. 2013

Am J Respir Cell Mol Biol

725

712

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The lung hosts multiple populations of macrophages and dendritic cells, which play a crucial role in lung pathology. The accurate identification and enumeration of these subsets are essential for understanding their role in lung pathology. Flow cytometry is a mainstream tool for studying the immune system. However, a systematic flow cytometric approach to identify subsets of macrophages and dendritic cells (DCs) accurately and consistently in the normal mouse lung has not been described. Here we developed a panel of surface markers and an analysis strategy that accurately identify all known populations of macrophages and DCs, and their precursors in the lung during steady-state conditions and bleomycin-induced injury. Using this panel, we assessed the polarization of lung macrophages during the course of bleomycin-induced lung injury. Alveolar macrophages expressed markers of alternatively activated macrophages during both acute and fibrotic phases of bleomycin-induced lung injury, whereas markers of classically activated macrophages were expressed only during the acute phase. Taken together, these data suggest that this flow cytometric panel is very helpful in identifying macrophage and DC populations and their state of activation in normal, injured, and fibrotic lungs.Keywords: pulmonary macrophages; alveolar macrophages; interstitial macrophages; macrophage polarization; lung fibrosis Cells of the innate immune system, and especially myeloid cells such as neutrophils, eosinophils, monocytes, macrophages (alveolar and interstitial), and dendritic cells (DCs, i.e., plasmacytoid DCs, CD1031 DCs, and CD11b 1 DCs), play an important role in lung development and physiology, and contribute to important lung diseases, including pulmonary infection, cancer, asthma, chronic obstructive pulmonary disease, and pulmonary fibrosis (1-5). Alveolar and interstitial lung macrophages exhibit different origins and life spans in lungs, and have been identified as key regulators of pathological and reparative processes. Alveolar macrophages, which are considered tissue-resident macrophages, populate lung tissue during early embryogenesis and remain viable for prolonged periods, with minimal replenishment from bone marrow-derived monocytes (6). In contrast, interstitial macrophages originate from bone marrow-derived monocytes and have a shorter half-life (7,8). In recent studies, several groups of investigators suggested that these two populations of lung macrophages play opposing roles in lung injury. Alveolar macrophages appear to limit neutrophil influx into the lung during acute lung injury (9) or chronic exposure to organic dust (10), whereas interstitial macrophages promote neutrophil extravasation (11,12). An additional layer of complexity is added by the phenotypic plasticity of macrophages. Classically activated macrophages (sometimes referred to as M1-polarized) have been suggested to promote the development of acute lung injury, whereas alternatively activated macrophages (M2) may play a role in limiting or resolving lu...

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The role of dendritic cells in asthma

Cited by 109 publications

References 114 publications

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

CD80 and CD86 knockdown in dendritic cells regulates Th1/Th2 cytokine production in asthmatic mice

Deficiency of gp91phox Inhibits Allergic Airway Inflammation

Flow Cytometric Analysis of Macrophages and Dendritic Cell Subsets in the Mouse Lung

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