Epithelial Cell Regulation of Allergic Diseases

Gour, Naina; Lajoie, Stéphane

doi:10.1007/s11882-016-0640-7

Cited by 18 publications

(10 citation statements)

References 99 publications

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“…IL-33 is often grouped together with thymic stromal lymphopoietin (TSLP) and IL-25 as innate, epithelium-derived cytokines expressed at mucosal surfaces that promote type 2 immune responses 42 . However, IL-33 is the only one of the three that is stored in the nucleus as a pre-formed molecule bound to chromatin.…”

Section: Discussionmentioning

confidence: 99%

Chromatin regulates IL-33 release and extracellular cytokine activity

et al. 2018

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IL-33 is an epithelium-derived, pro-inflammatory alarmin with enigmatic nuclear localization and chromatin binding. Here we report the functional properties of nuclear IL-33. Overexpression of IL-33 does not alter global gene expression in transduced epithelial cells. Fluorescence recovery after photobleaching data show that the intranuclear mobility of IL-33 is ~10-fold slower than IL-1α, whereas truncated IL-33 lacking chromatin-binding activity is more mobile. WT IL-33 is more resistant to necrosis-induced release than truncated IL-33 and has a relatively slow, linear release over time after membrane dissolution as compared to truncated IL-33 or IL-1α. Lastly, IL-33 and histones are released as a high-molecular weight complex and synergistically activate receptor-mediated signaling. We thus propose that chromatin binding is a post-translational mechanism that regulates the releasability and ST2-mediated bioactivity of IL-33 and provide a paradigm to further understand the enigmatic functions of nuclear cytokines.

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Section: Discussionmentioning

confidence: 99%

Chromatin regulates IL-33 release and extracellular cytokine activity

et al. 2018

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“…This led to the hypothesis that repeated infections support a state of immune tolerance by inducing an "immune regulatory network" underpinned by the function of T regulatory cells and immuno-suppressive cytokines, like TGF-β and IL-10 (23). Additionally, hypersensitivity disorders are not simply driven by aberrant T helper cell responses, but also by multiple cells of the innate immune system including innate lymphoid cells (ILCs) (24,25), tissue resident macrophages (26), and epithelial cells (27), all of which potentially serve as targets for immune modulation by microbial infection. Importantly, many of these cells have early developmental origins, and as we will explore later, are likely to be targeted by inflammatory cues during in utero development.…”

Section: Beyond Th1/th2 Dichotomymentioning

confidence: 99%

Training the Fetal Immune System Through Maternal Inflammation—A Layered Hygiene Hypothesis

2020

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Over the last century, the alarming surge in allergy and autoimmune disease has led to the hypothesis that decreasing exposure to microbes, which has accompanied industrialization and modern life in the Western world, has fundamentally altered the immune response. In its current iteration, the "hygiene hypothesis" suggests that reduced microbial exposures during early life restricts the production and differentiation of immune cells suited for immune regulation. Although it is now well-appreciated that the increase in hypersensitivity disorders represents a "perfect storm" of many contributing factors, we argue here that two important considerations have rarely been explored. First, the window of microbial exposure that impacts immune development is not limited to early childhood, but likely extends into the womb. Second, restricted microbial interactions by an expectant mother will bias the fetal immune system toward hypersensitivity. Here, we extend this discussion to hypothesize that the cell types sensing microbial exposures include fetal hematopoietic stem cells, which drive long-lasting changes to immunity.

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“…Both cytokines act as amplifiers of the allergic inflammatory immune response [23,24] via the membrane receptors IL-33R and IL-17RA/IL-17RB, respectively, which are highly expressed in various immune cells, including ILC2s, MCs, basophils, DCs and macrophages [25][26][27][28][29]. In particular, IL-33 can stimulate MC degranulation [30] and release of IL-8 [31], IL-1B, IL-6, tumor necrosis factor-alpha (TNF-α), and chemokine (C-C motif) ligand (CCL) 2 [32], which lead to formation of leukotrienes and prostaglandins and can enhance the inflammatory environment in the lungs [33].…”

Section: Airway Epithelium As a Key Player In Orchestrating The Allermentioning

confidence: 99%

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

López-Rodríguez

Benedé

Barderas

et al. 2017

J Investig Allergol Clin Immunol

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Airway epithelium is the cellular structure with the greatest surface exposed to a plethora of environmental airborne substances, including microorganisms, respiratory viruses, air pollutants, and allergens. In addition to being a protective physical barrier at the air-liquid interface, the airway epithelium acts as an effective chemical and immunological barrier that plays a crucial role in orchestrating the immune response in the lungs, by supporting the activation, recruitment, and mobilization of immune cells. Airway epithelium dysfunction has been clearly associated with various airway inflammatory diseases, such as allergic asthma. Although it is not fully understood why a person develops respiratory allergy, a growing body of evidence shows that the nature of the host's immune response is strongly determined by the state of the airway epithelium at the time of contact with the inhaled allergen. Our review highlights the physiological state of airway epithelium as a key element in the development of allergy and, particularly, in exacerbation of asthma. We review the role of physiological oxidants as signaling molecules in lung biology and allergic diseases and examine how high exposure to air pollutants (eg, cigarette smoke and diesel particles) can contribute to the increased incidence of respiratory allergy and exacerbation of the disease. Key words: Airway epithelium. Barrier dysfunction. Respiratory allergy. Redox biology. Air pollutants. ResumenEl epitelio pulmonar constituye la barrera celular más susceptible a la acción deletérea de la multitud de agentes que se encuentran en el ambiente, incluidos los alérgenos. Además de prevenir su acceso al organismo, la barrera epitelial de las vías respiratorias juega un papel inmunomodulador crucial, regulando de forma local la acción de las células del sistema inmune subyacentes. Una disfunción epitelial, provocada tanto directa como indirectamente por la acción de los aeroalérgenos, parece ser una de las causas principales de desregulación de la homeostasis pulmonar, causando una respuesta proinflamatoria descontrolada que cada vez más autores atribuyen al origen de las reacciones alérgicas. En esta revisión se quiere destacar el papel de la barrera epitelial pulmonar como regulador de la respuesta inmune en el contexto de la alergia. Las enfermedades crónicas que afectan a las vías respiratorias, tales como el asma alérgica, muestran frecuentemente una función epitelial defectuosa, apoyando así la hipótesis antes mencionada que subyace al origen de la alergia. El impacto de otros contaminantes ambientales -como virus respiratorios, bacterias, humo del tabaco y partículas diésel-sobre la integridad epitelial, así como su influencia en la biología redox pulmonar relacionada con el desarrollo de la respuesta alérgica, también se abordarán en la presente revisión.

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Epithelial Cell Regulation of Allergic Diseases

Cited by 18 publications

References 99 publications

Chromatin regulates IL-33 release and extracellular cytokine activity

Chromatin regulates IL-33 release and extracellular cytokine activity

Training the Fetal Immune System Through Maternal Inflammation—A Layered Hygiene Hypothesis

Airway Epithelium Plays a Leading Role in the Complex Framework Underlying Respiratory Allergy

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