Article

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

ABSTRACT

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
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    • "Cellular composition is important because the specialized secretory and ciliated cells produce mucus and antimicrobial agents and remove entrapped particles from the lung. Airway epithelial cells can also produce immune modulators, a function shared with the monocyte-derived cells intercalated within the surface layer (Hallstrand et al., 2014;Hammad and Lambrecht, 2008;Persson et al., 2014). Given these multiple functions it is critical that the cellular composition and architecture of the airway epithelium is quickly repaired after damage caused by viral or bacterial infection, or by inhalation of smoke or toxic gases (reviewed in (Hogan et al., 2014)). "
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    ABSTRACT: The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, while exogenous BMP4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this is break is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal critical roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium.
    Full-text · Article · Jan 2016 · Development
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    • "Cellular composition is important because the specialized secretory and ciliated cells produce mucus and antimicrobial agents and remove entrapped particles from the lung. Airway epithelial cells can also produce immune modulators, a function shared with the monocyte-derived cells intercalated within the surface layer (Hallstrand et al., 2014;Hammad and Lambrecht, 2008;Persson et al., 2014). Given these multiple functions it is critical that the cellular composition and architecture of the airway epithelium is quickly repaired after damage caused by viral or bacterial infection, or by inhalation of smoke or toxic gases (reviewed in (Hogan et al., 2014)). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The pseudostratified epithelium of the lung contains ciliated and secretory luminal cells and basal stem/progenitor cells. To identify signals controlling basal cell behavior we screened factors that alter their self-renewal and differentiation in a clonal organoid (tracheosphere) assay. This revealed that inhibitors of the canonical BMP signaling pathway promote proliferation but do not affect lineage choice, while exogenous BMP4 inhibits proliferation and differentiation. We therefore followed changes in BMP pathway components in vivo in the mouse trachea during epithelial regeneration from basal cells after injury. The findings suggest that BMP signaling normally constrains proliferation at steady state and this is break is released transiently during repair by the upregulation of endogenous BMP antagonists. Early in repair the packing of epithelial cells along the basal lamina increases, but density is later restored by active extrusion of apoptotic cells. Systemic administration of the BMP antagonist LDN-193189 during repair initially increases epithelial cell number but, following the shedding phase, normal density is restored. Taken together, these results reveal critical roles for both BMP signaling and cell shedding in homeostasis of the respiratory epithelium.
    Full-text · Article · Jan 2016 · Development
    • "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.
    No preview · Article · Jun 2015 · Toxicological Sciences
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