Innate Cells and T Helper 2 Cell Immunity in Airway Inflammation

Department of Medicine, Harvard Medical School, and Division of Rheumatology, Immunology, and Allergy, Brigham and Women's Hospital, Boston, MA 02115, USA.
Immunity (Impact Factor: 21.56). 09/2009; 31(3):425-37. DOI: 10.1016/j.immuni.2009.08.014
Source: PubMed


Activated mast cells, eosinophils, and basophils infiltrate the airways of asthmatics as a result of an overexuberant T helper 2 (Th2) cell immune response that drives the production of IgE, primes mast cells and basophils, and promotes tissue eosinophilia and mast cell hyperplasia. Recent evidence demonstrates that these innate effectors can be activated outside of this classical Th2 cell paradigm and that they have additional roles in promoting the development of innate and adaptive pulmonary inflammation. There is also an appreciation for the role of airway epithelial cells in orchestrating allergic pulmonary inflammation. Emerging data from basic research highlight the involvement of many unique pathways in the inflammation triggered by complex native allergens and microbes at the airway mucosal surface. Here, we review the role of effector cells and airway epithelial cells in augmenting and, at times, bypassing traditional Th2 cell-mediated allergic inflammation.

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Available from: K. Frank Austen, Sep 23, 2014
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    • "During allergic sensitization, inhaled allergens are taken up by antigen-presenting dendritic cells in the airway and presented to T-cells.18 The cytokine milieu leads to T-helper cell differentiation and production of IL-4, IL-5, and IL-13, resulting in immunoglobulin (Ig)E class switching, eosinophil recruitment, mucus production, airway hyperresponsiveness, and remodeling features.19,20 IL-5 is a critical cytokine for eosinophil generation in the bone marrow, as well as eosinophil recruitment, activation, and survival. "
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    ABSTRACT: Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma.
    Journal of Asthma and Allergy 04/2014; 7(7):53-65. DOI:10.2147/JAA.S39119
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    • "Mast cells are effector cells that display various functions during immune response and regulate allergic inflammation, such as, those associated with asthma, atopic dermatitis, and sinusitis. Activated mast cells release pro-inflammatory cytokines, such as, tumour necrosis factor (TNF)-α, interleukin (IL)-6, IL-8, IL-13, and inflammatory mediators, including histamine, leukotrienes, serotonin, prostaglandin (PG)E2, and PGD2 (Barrett and Austen, 2009; Mukherjee and Zhang, 2011). The expressions of proinflammatory cytokines depend on the activations of the transcription factor, nuclear factor- κB (NF-κB), and mitogen-activated protein kinases (MAPKs), such as, extracellular signal-regulated kinase (ERK), p38, stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK) (Jeong et al., 2003; Rasheed et al., 2009). "
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    ABSTRACT: Emodin, a naturally occurring anthraquinone derivative isolated from Polygoni cuspidati radix, has several beneficial pharmacologic effects, which include anti-cancer, anti-diabetic, and anti-inflammatory activities. In this study, the authors examined the effect of emodin on the production of proinflammatory cytokines, such as, tumor necrosis factor (TNF)-α and interleukin (IL)-6, in mouse bone marrow-derived mast cells (BMMCs) stimulated with phorbol 12-myristate 13-acetate (PMA) plus the calcium ionophore A23187. To investigate the mechanism responsible for the regulation of pro-inflammatory cytokine production by emodin, the authors assessed its effects on the activations of transcriptional factor nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs). Emodin attenuated the nuclear translocation of (NF)-κB p65 and its DNA-binding activity by reducing the phosphorylation and degradation of IκBα and the phosphorylation of IκB kinase B (IKK). Furthermore, emodin dose-dependently attenuated the phosphorylations of MAPKs, such as, extracellular signal-regulated kinase 1/2 (ERK1/2), p38 MAP kinase, and the stress-activated protein kinases (SAPK)/c-Jun-N-terminal kinase (JNK). Taken together, the findings of this study suggest that the anti-inflammatory effects of emodin on PMA plus A23187-stimulated BMMCs are mediated via the inhibition of NF-κB activation and of the MAPK pathway.
    Biomolecules and Therapeutics 11/2013; 21(6):435-441. DOI:10.4062/biomolther.2013.068 · 1.73 Impact Factor
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    • "The other possible mechanism by which eosinophils contribute to the airway disease of asthma may be by adhesion to and then migrating across vascular endothelial cells. These processes are largely regulated by cytokines/chemokines produced by a variety of cells, including T-helper 2 (Th2) cells (Barrett and Austen, 2009 ▶). Not only eosinophilic inflammation but also neutrophilic inflammation may play roles in severe asthma, so that infiltration of these two cell types is increased into the airways of asthmatic patients. "
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    ABSTRACT: Objective: Asthma is a chronic inflammatory disease of the respiratory airways distinguished by edema and infiltration of inflammatory immune cells. To test our hypothesis about the anti-inflammatory effect of saffron, we examined effects of Crocus sativus (C. sativus) extract as a prophylactic anti-inflammatory agent in sensitized rats. Materials and Methods: To induce experimental asthma, rats were sensitized with injection and inhalation of ovalbumin (OA). Forty male Wistar rats were divided into 5 groups (n=8 for each): control, sensitized (asthma), and sensitized and pretreated with three different concentrations of extract, 50, 100, and 200 mg/kg, 2 times a week (group asthma+50EX, group asthma+100EX, and group asthma+200EX). After 32 days, total white blood cells (WBC) counts, red blood cells (RBC), and platelet counts in blood were examined. Results: Total WBC number and eosinophil and neutrophil percentage in blood were increased, but lymphocyte decreased in sensitized animals compared with those of control group (p<0.05 to p<0.001). We observed also elevated levels in RBC and platelet counts after sensitization in the asthma group. Pretreatment of sensitized rats in all concentrations decreased WBC count which was significant in first two concentrations (p<0.01 compared with group asthma). All concentrations of extract decreased eosinophil percentage significantly (p<0.001 compared with group asthma), however, for neutrophil percentage this improvement was not significant. Lymphocyte percentage increased in group asthma+100EX compared with group asthma (p<0.05). Moreover, in all concentrations, the extract reduced RBC and platelet count in pretreated sensitized rats compared with group asthma (p<0.01 to p<0.001). Conclusion: Our findings indicated that the extract of C. sativus could be useful to prevent asthma as an anti-inflammatory treatment.
    Avicenna Journal of Phytomedicine 02/2013; 3(3):279-87.
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