Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity

Kato, Atsushi; Schleimer, Robert P.

doi:10.1016/j.coi.2007.08.004

Cited by 293 publications

(263 citation statements)

References 73 publications

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“…35,36 An interaction between the apical pole of the airway epithelium and luminal microbial antigens may induce the release of cytokines that trigger GCH via local stimulation or recruitment of additional inflammatory cells. 38 However, the close vicinity detected in our LPS model between bronchiole goblet cells and interstitial macrophages allow us to hypothesize that-beside any direct cell-cell interaction-soluble factors released by those macrophages may contribute also to modulate via a basolateral pathway the phenotype of bronchiolar goblet cells. Because of structural differences between the rat and human airway mucosal immune systems represented by the absence of BALT in healthy humans, 43 we decided to further validate our hypothesis in a human-based model rather than in rats stimulating in-vitro primary culture of HBEC with supernatants from human MDM challenged with or without LPS.…”

Section: Discussionmentioning

confidence: 71%

“…1,11 These infections can be induced by different types of microbes that provide a wide source of antigenslike LPS from Gram-negative bacteria-able to provoke a quick innate response when recognized by the airway epithelium. 38 Moreover, inhalation of air contaminated with LPS is associated with airway obstruction and inflammation, 39 signs present in these respiratory disorders. Single intra-tracheal administration of LPS from P. aeroginosa or E. coli in rat and mouse has been extensively used to induce mucus production.…”

Section: Discussionmentioning

confidence: 99%

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Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

Silva

Berčík

2012

Laboratory Investigation

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Airway goblet cell hyperplasia (GCH)-detectable by mucin staining-and abnormal macrophage infiltrate are pathological features present in many chronic respiratory disorders. However, it is unknown if both factors are associated. Using in-vivo and in-vitro models, we investigated whether macrophages are related with GCH and changes in mucin immunophenotypes. Lung sections from Sprague-Dawley rats treated for 48 h with one intra-tracheal dose of PBS or LPS (n ¼ 4-6 per group) were immunophenotyped for rat-goblet cells, immune, and proliferation markers. Human monocytederived macrophages (MDM) were pre-treated with or without LPS, immunophenotyped, and their supernatant, as well as cytokines at levels equivalent to supernatant were used to challenge primary culture of normal human bronchus epithelial cells (HBEC) in air-liquid interface, followed by MUC5B and MUC5AC mucin immunostaining. An association between increased bronchiolar goblet cells and terminal-bronchiolar proliferative epithelial cells confirmed the presence of GCH in our LPS rat model, which was related with augmented bronchiolar CD68 macrophage infiltration. The in-vitro experiments have shown that MUC5AC phenotype was inhibited when HBEC were challenged with supernatant from MDM pre-treated with or without LPS. In contrast, TNF-a and interleukin-1b at levels equivalent to supernatant from LPS-treated MDM increased MUC5AC. MUC5B was induced by LPS, supernatant from LPS-treated MDM, a mix of cytokines including TNF-a and TNF-a alone at levels present in supernatant from LPS-treated MDM. We demonstrated that macrophages are related with bronchiolar GCH, and that they induced MUC5B and inhibited MUC5AC in HBEC, suggesting a role for them in the pathogenesis of airway MUC5B-related GCH. KEYWORDS: airways; cytokines; LPS; lung inflammation; TNF-alphaMucus is a gel that covers the airway epithelium and is constituted by different glycoproteins called mucins, which are secreted by goblet cells from submucosal glands and the airway epithelium. 1 Mucus dissolves noxious gases and entraps foreign particles and pathogens, facilitating their clearance by mucociliary transport as a mechanism of innate defense. 2 However, in chronic inflammatory respiratory diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF), there is a pathological goblet cell hyperplasia (GCH) and mucus hypersecretion that can generate airway occlusion, associated with morbidity and death. 1 The main gel-forming mucins found in human airways are MUC5B and MUC5AC. 1 In healthy individuals, low levels of MUC5B and MUC5AC can be detected in mucus; although MUC5B is mainly present in the submucosal glands and MUC5AC is predominantly distributed in the airway epithelium. 3 In baseline conditions of chronic inflammatory respiratory disorders, MUC5B and/or MUC5AC are increased in different compartments of the respiratory tract. [3][4][5][6] For example, MUC5B and MUC5AC are augmented in small airway lumen and epithelium from patients with advanced CF; 4 GC...

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Section: Discussionmentioning

confidence: 71%

Section: Discussionmentioning

confidence: 99%

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

Silva

Berčík

2012

Laboratory Investigation

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“…Emerging information about epithelial-derived cytokines such as IL-33, IL-25, and TSLP (51,52) sheds further light on the immunological mechanisms underlying the contribution of the epithelium to the inflammatory process. TSLP has been shown to be involved in the initiation of the atopic phenotype, both in mouse models (12)(13)(14) and in skin sections from AD patients (7).…”

Section: Discussionmentioning

confidence: 99%

Intradermal Administration of Thymic Stromal Lymphopoietin Induces a T Cell- and Eosinophil-Dependent Systemic Th2 Inflammatory Response

Jessup

Brewer²,

Ōmori

et al. 2008

The Journal of Immunology

101

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The epithelial-derived cytokine thymic stromal lymphopoietin (TSLP) is sufficient to induce asthma or atopic dermatitis-like phenotypes when selectively overexpressed in transgenic mice, or when driven by topical application of vitamin D3 or low-calcemic analogues. Although T and B cells have been reported to be dispensable for the TSLP-induced inflammation in these models, little is known about the downstream pathways or additional cell types involved in the inflammatory response driven by TSLP. To characterize the downstream effects of TSLP in vivo, we examined the effects of exogenous administration of TSLP protein to wild-type and genetically deficient mice. TSLP induced a systemic Th2 inflammatory response characterized by increased circulating IgE and IgG1 as well as increased draining lymph node size and cellularity, Th2 cytokine production in draining lymph node cultures, inflammatory cell infiltrates, epithelial hyperplasia, subcuticular fibrosis, and up-regulated Th2 cytokine and chemokine messages in the skin. Responses to TSLP in various genetically deficient mice demonstrated T cells and eosinophils were required, whereas mast cells and TNF-α were dispensable. TSLP-induced responses were significantly, but not completely reduced in IL-4- and IL-13-deficient mice. These results shed light on the pathways and cell types involved in TSLP-induced inflammation.

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“…The airway epithelium lining the respiratory tract not only represents the first barrier of defense against respiratory pathogens but is often the primary target of infection (1). Consequently, apart from a critical role in gas exchange function, airway epithelial cells additionally participate in host defense mechanisms by producing cytokines and chemokines (2)(3)(4)(5)(6)(7)(8). Since exacerbated responses by airway epithelial cells in response to innocuous antigens or pathogens can prove detrimental to lung function, airway epithelial cells have also evolved to regulate pulmonary homeostasis by multiple mechanisms, including, among others, expression of CD200 (9), MUC-1 (10), and surfactant proteins (11) and reduced expression of adaptor molecules (12)(13)(14).…”

mentioning

confidence: 99%

Local Blockade of Epithelial PDL-1 in the Airways Enhances T Cell Function and Viral Clearance during Influenza Virus Infection

McNally

Willette

et al. 2013

J Virol

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Beyond inflammation: airway epithelial cells are at the interface of innate and adaptive immunity

Cited by 293 publications

References 73 publications

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

Macrophages are related to goblet cell hyperplasia and induce MUC5B but not MUC5AC in human bronchus epithelial cells

Intradermal Administration of Thymic Stromal Lymphopoietin Induces a T Cell- and Eosinophil-Dependent Systemic Th2 Inflammatory Response

Local Blockade of Epithelial PDL-1 in the Airways Enhances T Cell Function and Viral Clearance during Influenza Virus Infection

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