Hammad H, Lambrecht BN.Dendritic cells and epithelial cells: linking innate and adaptive immunity in asthma. Nat Rev Immunol 8:193-204

Department of Respiratory Diseases, Laboratory of Immunoregulation and Mucosal Immunology, University Hospital Ghent, Belgium.
Nature Reviews Immunology (Impact Factor: 34.99). 04/2008; 8(3):193-204. DOI: 10.1038/nri2275
Source: PubMed


Dendritic cells (DCs) are generally held responsible for initiating and maintaining allergic T helper 2 (T(H)2)-cell responses to inhaled allergens in asthma. Although the epithelium was initially considered to function solely as a physical barrier, it is now seen as a central player in the T(H)2-cell sensitization process by influencing the function of DCs. Clinically relevant allergens, as well as known environmental and genetic risk factors for allergy and asthma, often interfere directly or indirectly with the innate immune functions of airway epithelial cells and DCs. A better understanding of these interactions, ascertained from human and animal studies, might lead to better prevention and treatment of asthma.

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Available from: Hamida Hammad, Jul 03, 2014
    • "These interactions occur both within organs of the immune system , such as thymus, lymph nodes, spleen, and bone marrow (Malhotra et al., 2013; Mueller and Germain, 2009; Roozendaal and Mebius, 2011), as well as within organs outside of the immune system including the lung (Hammad and Lambrecht, 2008), the gut (Peterson and Artis, 2014), the liver (Li and Tian, 2013), and the central nervous system (CNS; Sternberg, 2006). The interactions of immune cells with cells outside of the immune system shape the type of immune response, the response magnitude, and whether an immune response occurs. "
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    ABSTRACT: Immunotoxicology assessments have historically focused on the effects that xenobiotics exhibit directly on immune cells. These studies are invaluable as they identify immune cell targets and help characterize mechanisms and/or adverse outcome pathways of xenobiotics within the immune system. However, leukocytes can receive environmental cues by cell-cell contact or via released mediators from cells of organs outside of the immune system. These organs include, but are not limited to, the mucosal areas such as the lung and the gut, the liver, and the central nervous system. Homeostatic perturbation in these organs induced directly by toxicants can initiate and alter the outcome of local and systemic immunity. This review will highlight some of the identified nonimmune influences on immune homeostasis and provide summaries of how immunotoxic mechanisms of selected xenobiotics involve nonimmune cells or mediators. Thus, this review will identify data gaps and provide possible alternative mechanisms by which xenobiotics alter immune function that could be considered during immunotoxicology safety assessment. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Toxicological Sciences 06/2015; 145(2):214-32. DOI:10.1093/toxsci/kfv060 · 3.85 Impact Factor
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    • "Alveolar and bronchial epithelial cells can secrete a range of different cytokines upon exposure to foreign compounds that can promote an innate immune response, and in certain situations also specifically direct adaptive immune responses (Lambrecht and Hammad, 2008, 2010). Therefore, the current study investigated the immunomodulatory response of lung epithelial cells to different PAHs using the alveolar epithelial cell line A549. "
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    ABSTRACT: Studying the effects of hydrophobic chemicals using in vitro cell based methods is hindered by the difficulty in bringing and keeping these chemicals in solution. Their effective concentrations are often lower than their nominal concentrations. Passive dosing is one approach that provides defined and stable dissolved concentrations during in vitro testing, and was applied to control and maintain freely dissolved concentrations of polycyclic aromatic hydrocarbons (PAHs) at levels up to their aqueous solubility limit. The immunomodulatory effects of 9 different PAHs at aqueous solubility on human bronchial epithelial cells were determined by analysing the cytokine promoter expression of 4 different inflammatory cytokines using stably transfected recombinant A549 cell lines. Diverse immunomodulatory responses were found with the highest induction observed for the most hydrophophic PAHs chrysene, benzo(a)antracene and benzo(a)pyrene. Cytokine promoter expression was then studied in dose response experiments with acenaphthene, phenanthrene and benzo(a)anthracene. The strongest induction was observed for benzo(a)anthracene. Cell viability analysis was performed and showed that none of the PAHs induced cytotoxicity at any of the concentrations tested. Overall, this study shows that (1) immunomodulatory effects of PAHs can be studied in vitro at controlled freely dissolved concentrations, (2) the most hydrophobic PAHs were the strongest inducers and (3) induction was often higher at lower exposure levels and decreased then with concentration despite the apparent absence of cytotoxicity. Copyright © 2014. Published by Elsevier Ltd.
    Toxicology in Vitro 03/2015; 29(2):345-351. DOI:10.1016/j.tiv.2014.11.007 · 2.90 Impact Factor
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    • "Dendritic cells (DCs) are APCs that play an important role in modulating immune responses.20,21,22,23 DCs can be divided into immature and mature DCs. "
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    ABSTRACT: Purpose Bacillus Calmette-Guérin (BCG) is known to suppress the asthmatic responses in a murine model of asthma and to induce dendritic cells (DCs) maturation. Mature DCs play a crucial role in the differentiation of regulatory T cells (Tregs), which are known to regulate allergic inflammatory responses. To investigate whether BCG regulates Tregs in a DCs-mediated manner, we analyzed in a murine model of asthma. Methods BALB/c mice were injected intraperitoneally with BCG or intravenously with BCG-stimulated DCs and then sensitized and challenged with ovalbumin (OVA). Mice were analysed for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells in the bronchoalveolar lavage (BAL) fluid, and histopathological changes in the lung. To identify the mechanisms, IgE, IgG1 and IgG2a in the serum were analysed and the CD25+ Tregs in the mice were depleted with anti-CD25 monoclonal antibody (mAb). Results BCG and the transfer of BCG-stimulated DCs both suppressed all aspects of the asthmatic responses, namely, BHR, the production of total IgE and OVA-specific IgE and IgGs, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment reversed these effects. Conclusions BCG can attenuate the allergic inflammation in a mouse model of asthma by a Tregs-related mechanism that is mediated by DCs.
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